Xov xwm

Javascript tam sim no raug kaw hauv koj lub browser.Qee qhov nta ntawm lub vev xaib no yuav tsis ua haujlwm yog tias JavaScript raug kaw.
Sau npe nrog koj cov ntsiab lus tshwj xeeb thiab cov tshuaj tshwj xeeb ntawm kev txaus siab, thiab peb yuav phim cov ntaub ntawv koj muab nrog cov ntawv hauv peb cov ntaub ntawv dav dav thiab xa email rau koj daim ntawv PDF tam sim ntawd.
Ding Jingnuo, Zhao Weifeng, Department of Infectious Disease, Suzhou University First Affiliated Hospital, Suzhou City, Jiangsu Province, 215000 Tel.qog ntawm lub plab zom mov nrog 5-xyoo kev ciaj sia ntawm 14.1%.Ntau tus neeg mob nrog HCC raug kuaj pom nyob rau theem siab, yog li kev tshuaj xyuas ntxov yog qhov tseem ceeb los txo cov neeg tuag los ntawm HCC.Ntxiv nrog rau kev siv cov ntsuas ntsuas xws li ntshav alpha-fetoprotein (AFP), lens lectin-reactive alpha-fetoprotein (AFP-L3), thiab txawv txav prothrombin (vitamin K deficiency-induced protein II, PIVKA-II), kua dej biopsy. Nws tau raug pom tias yog tus nqi kuaj mob hauv kev tshawb pom ntawm HCC.Piv nrog rau cov txheej txheem invasive, kua biopsy tuaj yeem kuaj pom cov kab mob malignant metabolites.Cov txheej txheem ua kua dej biopsy tshawb xyuas cov qog hlwb, circulating qog DNA, circulating RNA, thiab exosomes thiab siv rau kev tshuaj ntsuam ntxov, kuaj mob, thiab kev soj ntsuam kev soj ntsuam ntawm HCC.Tsab ntawv xov xwm no tshuaj xyuas cov kab mob molecular thiab kev siv ntau yam kev ua kua dej biopsy los cais cov cim biomarkers uas yuav muaj txiaj ntsig zoo rau kev ntsuam xyuas ntxov ntawm HCC txhawm rau txhim kho kev tshuaj ntsuam ntxov ntawm pawg HCC uas muaj kev pheej hmoo siab.Cov lus tseem ceeb: kua dej biopsy txheej txheem, hepatocellular carcinoma, pab pawg muaj kev pheej hmoo siab.
Hepatocellular carcinoma (HCC) yog ib hom mob qog nqaij hlav ntawm lub plab zom mov, nyob rau qib thib rau ntawm cov neeg mob tshiab ntawm cov qog nqaij hlav hauv cov txiv neej thiab poj niam.1 Thoob plaws ntiaj teb, mob qog noj ntshav yog qhov thib peb ua rau mob qog noj ntshav tom qab mob qog noj ntshav thiab mob qog noj ntshav, suav txog 8.3% ntawm cov neeg mob qog noj ntshav tuag los ntawm tag nrho cov neoplasms malignant.1 Kev soj ntsuam ntawm HCC yog ze ze rau theem ntawm kev kuaj mob.Cov laj thawj tseem ceeb rau kev muaj sia nyob tsis zoo hauv HCC yog intrahepatic metastases, portal venous qog thrombi, thiab cov metastases nyob deb ntawm kev txiav txim siab, thiab ntau yam ntawm cov yam ntxwv no twb muaj nyob rau hauv cov neeg mob thaum lub sijhawm kuaj mob.
Raws li kev kuaj mob thiab cov txheej txheem kho mob, cov teeb meem tseem ceeb ntawm kev tsim HCC yog cirrhosis ntawm daim siab, kab mob siab B (HBV) lossis kab mob siab C (HCV) kab mob, kab mob ntawm lub siab muaj dej cawv, thiab kab mob tsis muaj dej cawv fatty siab (NAFLD. ).2 Tsis tas li ntawd, muaj feem cuam tshuam rau HCC suav nrog kev noj zaub mov tsis muaj kab mob aflatoxin, schistosomiasis, lwm yam ua rau cirrhosis, tsev neeg keeb kwm ntawm mob qog noj ntshav, ntshav qab zib, rog rog, haus luam yeeb, thiab tshuaj tua kab mob siab.35- thiab 45-xyoo-laus cov neeg muaj kev pheej hmoo siab yuav tsum tau mus kuaj mob tsis tu ncua.Kev tshuaj ntsuam xyuas ntxov yog ib qho tseem ceeb ntawm kev kho mob thaum ntxov los txhim kho tag nrho cov neeg muaj sia nyob nrog HCC.
Biomarkers xws li AFP, AFP-L3 thiab PIVKA-II raug pom zoo rau kev tshuaj xyuas ntxov ntawm HCC3,4.Cov txheej txheem ua kua biopsy tau pom cov txiaj ntsig tau zoo hauv kev kuaj mob ntxov thiab kev tshuaj xyuas kev kho mob.5,6 Kev nce qib tseem ceeb tau ua tiav hauv HCC kua biopsy, uas tej zaum yuav muaj kev nkag siab ntau dua thiab tshwj xeeb tshaj li cov khoom siv tshuaj pleev ib ce xws li AFP (Table 1).
AFP yog ib qho biomarker siv dav hauv HCC thiab tam sim no yog cov ncauj lus kom ntxaws tshaj plaws biomarker dav siv rau kev tshuaj ntsuam ntxov, kuaj mob, thiab ntsuas tus kab mob.Kev nce qib AFP tsis tu ncua yog suav tias yog qhov muaj feem pheej hmoo rau kev nce qib ntawm HCC.7,8 Qhov kev kuaj pom tus nqi ntawm me me hepatocellular carcinoma (sHCC) yog nce nrog kev txhim kho ntawm ultrasound thiab xam tomography, thiab AFP tau pom tias yog qhov tsis txaus ntseeg tshwj xeeb rau kev kuaj xyuas hHCC hauv kev kho mob.Raws li kev tshawb fawb rov qab los ntawm ntau qhov chaw kawm 9, AFP qhov zoo tau pom nyob rau hauv 46% (616/1338) ntawm HCC cov neeg mob thiab 23.4% (150/641) ntawm cov neeg mob sHCC.Tsis tas li ntawd, AFP qib tau nce siab hauv cov neeg mob uas muaj kab mob siab ntev thiab cirrhosis.10 Yog li, AFP muaj qee qhov kev tshuaj ntsuam xyuas rau sHCC.11 Raws li Asia-Pacific Clinical Practice Guidelines for Hepatocellular Carcinoma, kev siv AFP tsis pom zoo.12 Cov ntaub ntawv pov thawj kho mob qhia tias PIVKA-II yog qhov zoo tshaj rau AFP hauv kev kho HCC thiab kev sib xyaw ntawm PIVKA-II thiab AFP muaj. tus nqi diagnostic ntau dua hauv HCC.Piv nrog rau cov ntaub so ntswg biopsy, kua biopsy feem ntau pom cov qog nqaij hlav hauv cov kua dej hauv lub cev (ntshav, qaub ncaug, kua pleural, kua cerebrospinal, lossis zis) thiab tsis tshua nkag mus rau cov ntaub so ntswg.14 Tsis tas li ntawd, cov kua dej biopsies tuaj yeem cuam tshuam cov yam ntxwv tsis zoo uas tsis muaj nyob hauv cov qog nqaij hlav.15 Cov kua dej biopsies tseem tsis tau raug kuaj hauv kev kho mob rau txhua hom qog nqaij hlav, tab sis lawv qhov kev kuaj mob muaj peev xwm ua rau mob qog noj ntshav tau nyiam cov kws kho mob oncologist.16 Fluid biopsy tuaj yeem kuaj pom cov qog hlwb (CTCs), cov qog DNA (cDNA), circulating dawb RNA (ecRNA), thiab exosomes.Hauv tsab xov xwm no, peb yuav tham txog cov yam ntxwv, lub luag haujlwm, thiab kev siv ntau yam kev ua kua dej biopsy hauv kev tshuaj ntsuam ntxov ntawm pawg HCC uas pheej hmoo siab.
Extracellular DNA (cfDNA) hauv cov ntshav kuaj los ntawm cov neeg noj qab haus huv tau piav qhia thawj zaug hauv xyoo 1948 los ntawm Mandel li al.17 cfDNA yog ib qho cell-dawb DNA tawg thaj tsam li 160-180 bp nyob rau hauv ntev, pib los ntawm lymphocytes thiab myeloid hlwb.ctDNA yog ib qho kev hloov pauv DNA tshwj xeeb tso tawm los ntawm cov qog hlwb rau hauv cov ntshav peripheral, uas sawv cev rau cov ntaub ntawv genomic ntawm cov qog hlwb tom qab qee cov txheej txheem pathophysiological, suav nrog necrosis, apoptosis, thiab excretion.Qhov kev faib ua feem ntawm ctDNA nyob rau hauv tag nrho cfDNA sib txawv nrog cov qog nqaij hlav, thiab cDNA fragments tau tshaj tawm tias feem ntau yuav tsawg dua 167 bp ntev.18 Underhill txoj kev tshawb fawb pom tias cfDNA fragments feem ntau luv dua li ib txwm cfDNA.19 Piv nrog rau cov tib neeg noj qab haus huv, tag nrho ntev ntawm cfDNA fragments hauv cov ntshav ntawm cov neeg mob qog noj ntshav yog luv, yog li cfDNA tuaj yeem siv los ua qhov qhia txog kev kuaj qog nqaij hlav ntxov.Kev ua kom muaj txiaj ntsig ntawm qee qhov ntawm cfDNA fragment lengths tuaj yeem txhim kho kev tshawb pom ntawm cDNA cuam tshuam nrog cov qog nqaij hlav tsis-metastatic.Cov kev tshawb fawb tau pom tias ctDNA pom muaj nyob hauv ntau dua 75% ntawm cov kab mob pancreatic, hnyuv, zais zis, plab hnyuv, siab, zes qe menyuam, mis, melanoma, thiab mob qog noj ntshav hauv lub taub hau thiab caj dab.20,21 Txawm li cas los xij, tus nqi ntawm ctDNA hauv cov ntshav nyob ntawm qhov chaw ntawm cov qog.22 Hauv kev tshawb fawb los ntawm Bettegoud, cov neeg mob uas muaj kab mob plab, lub mis, lub siab, lub ntsws, thiab cov qog nqaij hlav prostate tau pom tias muaj cDNA ntau dua hauv lawv cov ntshav dua li lwm cov qog nqaij hlav.Hauv qhov sib piv, hauv cov neeg mob qog noj ntshav hauv qhov ncauj, mob qog noj ntshav pancreatic, mob plab hnyuv, thiab glioma, cDNA concentration hauv cov ntshav qis dua.nees nkaum ib
Vim tias ctDNA muaj tib yam kev hloov pauv caj ces raws li cov qog nqaij hlav hauv thawj, cDNA tuaj yeem siv los txheeb xyuas cov qog nqaij hlav tshwj xeeb thiab kev hloov pauv ntawm epigenetic, suav nrog cov tshuaj methylation, hydroxymethylation, ib qho nucleotide variations, thiab luam cov lej variations.nees nkaum peb
DNA methylation yog ib qho ntawm feem ntau cov kev hloov pauv epigenetic uas ua rau muaj kev cuam tshuam cov noob.Piv nrog rau cov hlwb ib txwm muaj, muaj qhov sib txawv ntawm tag nrho cov theem ntawm methylation ntawm cov qog cell genome, tshwj xeeb tshaj yog nyob rau hauv methylation ntawm cov qog suppressor noob, uas tuaj yeem kuaj pom thaum ntxov, qhia tias kev hloov pauv hauv DNA methylation yuav yog qhov qhia txog thaum ntxov. nrhiav pom ntawm tumorigenesis.Cov qog nqaij hlav qog nqaij hlav cuam tshuam nrog HCC tuaj yeem ua tsis tau los ntawm kev txhawb nqa methylation, yog li txhawb cov qog nqaij hlav.24 DNA methylation yog qhov cim zoo rau kev kuaj mob ntxov ntawm cov qog vim nws cov ntaub so ntswg tshwj xeeb, kuaj pom, thiab muaj hnub nyoog ywj pheej.Tsis tas li ntawd, DNA methylation muaj ntau dua piv rau kev hloov pauv ntawm somatic vim tias muaj ntau lub hom phiaj thiab ntau qhov chaw hloov CpG hauv txhua cheeb tsam ntawm lub hom phiaj genome.25 Ntxiv rau ntau qhov chaw CpG, ntau tus neeg sab nraud hypermethylated loci hauv ctDNA tau txheeb xyuas hauv DBX2, THY1, MT1M, INK4A, VIM, FBLN1, thiab RGS10.26 Xu et al.Kev sib piv ntawm cfDNA cov qauv los ntawm 1098 HCC cov neeg mob thiab 835 kev tswj kev noj qab haus huv yog cov noob muaj feem xyuam nrog HCC tau pom tias muaj kev sib raug zoo nrog cov plasma cDNA methylation kos npe.25 Raws li kev soj ntsuam hauv chav kuaj, cov qauv kev kwv yees tau tsim muaj 10 cov cim methylation nrog rhiab heev thiab qhov tshwj xeeb ntawm 85.7% thiab 94.3%, feem, thiab cov cim no muaj feem cuam tshuam nrog cov qog loj, qog theem, thiab cov lus teb rau kev kho mob.Cov txiaj ntsig no qhia tau hais tias kev siv cDNA methylation markers tuav cov lus cog tseg zoo hauv kev kuaj mob, saib xyuas, thiab kev kwv yees ntawm HCC.Hauv cov qauv methylation uas muaj peb yam tsis zoo methylated noob (APC, COX2, RASSF1A) thiab ib qho miRNA (miR203) nthuav tawm los ntawm Lu et al27, qhov rhiab heev thiab qhov tshwj xeeb ntawm qauv 27 rau kev kuaj HBV-txuas nrog HCC yog sib piv.80%.Tsis tas li ntawd, tus qauv tuaj yeem kuaj pom 75% ntawm cov neeg mob uas tsis tau kuaj pom HCC nrog AFP qib ntawm 20 ng / mL.Cov noob rau Ras-associated domain family 1A protein (RASSF1A) yog qhov tseem ceeb ntawm DNA rov ua ntu zus hauv tib neeg genome.Araujo et al.xaus lus tias hypermethylation ntawm RASSF1A tus txhawb nqa tuaj yeem yog biomarker muaj txiaj ntsig rau kev tshuaj xyuas ntxov ntawm HCC thiab lub hom phiaj molecular rau kev kho epigenetic.28 Hauv ib txoj kev tshawb fawb, cov ntshav RASSF1A txhawb nqa hypermethylation tau pom hauv 73.3% ntawm cov neeg mob HCC.29 Ntev interspersed nucleotide caij 1 (LINE-1) yog lwm tus neeg sib tw ua haujlwm retrotransposition.Hypomethylation ntawm LINE-1 tau pom nyob rau hauv DNA ntawm 66.7% ntawm HCC cov ntshav kuaj thiab tau cuam tshuam nrog kev rov tshwm sim ntxov thiab tsis muaj sia nyob tom qab radical resection.29 Hypermethylation yog ib qho txheej txheem caj ces uas ua lub luag haujlwm tshwj xeeb hauv kev txhim kho daim siab cirrhosis thiab HCC.30 Nyob rau hauv sib piv, hydroxymethylation yog ib tug demethylation txheej txheem uas induces gene reactivation thiab qhia, thiab nrhiav tau ntawm 5-hydroxymethylcytosine (5-hmC) khoom nyob rau hauv cov txheej txheem no yuav siv tau los txheeb xyuas cov qog.Methylation thiab hydroxymethylation ntawm cDNA yog txuam nrog cov qog nqaij hlav thiab tuaj yeem ua rau muaj kev tshuaj xyuas ntxov ntawm HCC.Hauv kev tshawb fawb ntawm 2554 cov ntsiab lus, 31 genome-wide 5-hmCs tau pom nyob rau hauv cov qauv cfDNA, thiab 32 cov noob tau txheeb xyuas los ntawm kev sib piv 5-hmC sib lawv liag hauv HCC cov neeg mob thiab cov neeg muaj kev pheej hmoo siab xws li cov kab mob ntev.Diagnostic qauv ntawm daim siab kab mob.thiab cirrhosis.Cov qauv no tau zoo tshaj rau AFP hauv kev paub qhov txawv HCC los ntawm cov ntaub so ntswg uas tsis yog qog.
Kev hloov pauv hauv cov cheeb tsam coding tuaj yeem ua rau muaj qhov txawv txav, uas tuaj yeem ua rau muaj kev hloov pauv hauv cov protein ntau thiab thaum kawg mob qog noj ntshav.Ib leeg nucleotide variants yog cov cim genomic tseem ceeb rau kev tshuaj ntsuam qog thaum ntxov vim lawv cov ntaub so ntswg muaj kev ntseeg siab thiab cov qog nqaij hlav thiab cov nqaij mos.Ntau cov kev tshawb fawb txog HCC uas siv cov tiam tom ntej sequencing (NGS) rau exome thiab tag nrho genome sequencing ntawm mob qog noj ntshav tau txheeb xyuas cov kab mob sib hloov ntawm tes xws li TP53 thiab CTNNB1, nrog rau ntau yam xws li ARID1A, MLL, IRF2.Cov noob tshiab, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3 thiab JAK1 qhia cov kev hloov pauv nruab nrab. Mutant gene function analysis qhia tias kev hloov pauv hauv chromatin remodeling, Wnt / β-catenin thiab JAK / STAT teeb liab hloov, P53-cell voj voog txoj hauv kev, epigenetic modifiers, oxidative kev nyuaj siab, txoj kev PI3K / AKT / MTOR thiab RAS / RAF / MAPK kinase txoj hauv kev ua lub luag haujlwm tseem ceeb hauv HCC oncogenesis.32,33 Hauv kev tshawb fawb uas kuaj pom cov qog nqaij hlav sib txuas, Huang li al pom tias qhov zaus ntawm cov qog muaj feem cuam tshuam nrog ctDNA yog 19.5%, thiab qhov tshwj xeeb yog 90%. .34 Tsis tas li ntawd, cov neeg mob uas muaj kev cuam tshuam ntawm vascular invasion feem ntau yuav muaj ctDNA kev hloov pauv (P = 0.041) thiab luv dua rov qab tsis muaj sia nyob (P<0.001). Mutant gene function analysis qhia tias kev hloov pauv hauv chromatin remodeling, Wnt / β-catenin thiab JAK / STAT teeb liab hloov, P53-cell voj voog txoj hauv kev, epigenetic modifiers, oxidative kev nyuaj siab, txoj kev PI3K / AKT / MTOR thiab RAS / RAF / MAPK kinase txoj hauv kev ua lub luag haujlwm tseem ceeb hauv HCC oncogenesis.32,33 Hauv kev tshawb fawb uas kuaj pom cov qog nqaij hlav sib txuas, Huang li al pom tias qhov zaus ntawm cov qog muaj feem cuam tshuam nrog ctDNA yog 19.5%, thiab qhov tshwj xeeb yog 90%. .34 Tsis tas li ntawd, cov neeg mob uas muaj kev cuam tshuam ntawm vascular invasion feem ntau yuav muaj ctDNA kev hloov pauv (P = 0.041) thiab luv dua rov qab tsis muaj sia nyob (P<0.001).Mutant gene function analysis qhia tias kev hloov pauv hauv chromatin remodeling, Wnt / β-catenin thiab JAK / STAT signaling, P53 cell cycle pathway, epigenetic modifiers, oxidative stress pathways, PI3K/AKT/MTOR pathway, thiab RAS/RAF/MAPK kinase pathway plays Lub luag haujlwm tseem ceeb hauv HCC tumorigenesis.32,33 Hauv kev tshawb fawb uas pom cov qog muaj feem cuam tshuam txog kev hloov pauv, Huang et al.pom tias qhov zaus ntawm ctDNA-dependent qog-associated mutations yog 19.5% thiab qhov tshwj xeeb yog 90%..34 Кроме того, у пациентов с сосудистой инвазией чаще встречались мутации цДНК (P=0,041) вь кржией чаще встречались мутации цДНК (P=0,041) вь кржоле и боле 0,041. .34 Tsis tas li ntawd, cov neeg mob vascular invasion muaj ntau dua cDNA mutations (P = 0.041) thiab tsis muaj kab mob luv luv (P<0.001).Kev ua haujlwm ntawm cov noob caj noob ces qhia txog kev hloov kho chromatin, Wnt / β-catenin thiab JAK / STAT signaling, P53 cell cycle pathway, epigenetic modifiers, oxidative stress pathway, PI3K/AKT/MTOR pathway, thiab RAS/RAF/MAPK kinase txoj kev ua lub luag haujlwm tseem ceeb hauv oncogenesis ntawm HCC. 32,33 在 检测 到 相关 突变 的 研究 研究 的 发现 发现 发现 人 相关 依赖于 依赖于 依赖于 依赖于 依赖于 依赖于 依赖于 为 为 为 为 为 为 为 为 为 为 为 为 为 为 90% .34 经历, 经历 的 的 患者 患者 患者 患者 有 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生发生 发生突变（P=0.041）和更短的无复发生存期（P<0.001）. 32.3 在在 检测一 相关检测 突变相关 突变 的的 研究等 肿瘤等 肿瘤 相关 依赖于 依赖于 依赖于 依赖于 依赖于 依赖于 为 为 为 为 为 为 为 为 为 为 侵犯 血管 侵犯更 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 Ctdna 发生 (P = 0.041) 和短的无复发生存期 (P<0.001).32,33 Nyob rau hauv ib txoj kev tshawb nrhiav pom cov qog nqaij hlav sib txuas, Huang li al.pom tias cov qog nqaij hlav sib txuas yog 19.5% nyob ntawm cDNA nrog qhov tshwj xeeb ntawm 90% 34. Tsis tas li ntawd, cov neeg mob uas tau raug mob vascular invasion feem ntau yuav tsim cDNA.мутация (P = 0,041) и более короткая безрецидивная выживаемость (P <0,001). Kev hloov pauv (P = 0.041) thiab luv luv tsis muaj kab mob ciaj sia (P<0.001).Lwm hom HCC tsav tsheb yog TP53, uas muaj qhov hloov pauv ntawm ntau dua 30%.Cov kev tshawb fawb tau pom tias qhov zaus ntawm TP53 kev hloov pauv hauv ctDNA hauv cov ntshav thiab zis yog li ntawm 5% txog 60%.35 Johan txoj kev tshawb fawb tau pom tias ctDNA kev hloov pauv spectrum hauv lig HCC muaj qhov hloov pauv zoo sib xws rau HCC thaum ntxov, suav nrog TERT txhawb nqa (51%), TP53 (32%), CTNNB1 (17%), PTEN (8%), kev hloov pauv hauv AXIN 1., ARID2, KMT2D thiab TSC2 (6% txhua).36 Lub β-catenin (CTNNB1) oncogene plays lub luag haujlwm tseem ceeb hauv Wnt signaling pathway.Lub transcription coactivator CTNNB1 tuaj yeem txhawb nqa cov noob qhia, uas tuaj yeem ua rau cov cell proliferation, inhibition of apoptosis, thiab angiogenesis.CTNNB1 tseem tuaj yeem cuam tshuam nrog TERT los txhawb kev hloov pauv hepatocyte.33 Tus neeg txhawb nqa TERT feem ntau hloov pauv hauv qee cov qog nqaij hlav.Kev hloov pauv hauv TERT, yog ib qho kev hloov pauv caj ces ntxov tshaj plaws hauv kev hloov pauv tsis zoo ntawm HCC, tuaj yeem ua rau telomerase reactivation hauv cirrhotic hepatocytes thiab tuaj yeem txhawb kev loj hlob thiab tiv thaiv kev laus.Kev hloov pauv hauv 33-37 TERT tus txhawb nqa tau tshaj tawm tias tshwm sim hauv 59-90% ntawm cov neeg mob uas muaj lub siab proliferative nodules thiab HCC thaum ntxov thiab cuam tshuam nrog kev ciaj sia.38
Cov lej hloov pauv (CNA) yog ib qho tseem ceeb subtype ntawm somatic mutations.Kev tshawb fawb tau pom tias qhov dav thiab lub nra hnyav ntawm CNA yog ib qho kev kos npe genomic muaj peev xwm los kwv yees qog lub cev tiv thaiv kab mob thiab tsis suav nrog qee hom mob qog noj ntshav.39 Active infiltration signaling, siab cytolytic kev ua, mob hnyav thiab cov cim caj ces cuam tshuam nrog kev nthuav qhia antigen hauv HCC.Kev soj ntsuam ntawm cov ntaub ntawv array ntawm ib leeg nucleotide polymorphisms hauv 477 cov ntsiab lus tau qhia txog lub nra hnyav ntawm CNS.Nyob rau hauv sib piv, chromosomally unstable qog nrog ib tug siab uas nws kim heev CNA load pom cov cim ntawm lub cev tsis muaj zog thiab tau txuam nrog proliferation, DNA kho, thiab TP53 dysfunction.Xu et al.qhia tias pawg HCC muaj cov qhab nia CNA siab dua li pab pawg kab mob siab.40 Siv tag nrho-genome sequencing ntawm ib lub xov tooj ntawm tes, CNAs tau pom tshwm sim thaum ntxov hauv hepatocarcinogenesis thiab nyob ruaj khov thaum lub sij hawm qog nqaij hlav.41 Chung et al.pom tias cov qib cfDNA tau nce siab hauv cov neeg mob HCC thiab cov genome-wide CNAs hauv cfDNA yog ib qho tseem ceeb ntawm kev soj ntsuam xyuas tus cim hauv HCC cov neeg mob kho nrog sorafenib.42 Cov neeg mob uas muaj CNA lub nra hnyav dua yuav muaj kev kis kab mob thiab tuag ntau dua li cov uas muaj CNA lub nra qis dua.Ollerich et al.pom tias daim ntawv luam tus lej tsis ruaj khov (CNI) tuaj yeem siv los ntsuas CNA hauv cfDNA ntawm cov neeg mob qog noj ntshav.Lawv tau sau tseg tias cov neeg mob uas mob qog noj ntshav tau nce siab CNI cov qhab nia ntau dua li pawg tswj hwm, uas ntsuas cov neeg mob cov lus teb rau kev siv tshuaj khomob thiab kev tiv thaiv kab mob.43 Cov txiaj ntsig no qhia tias CNAs pom nyob rau hauv cov kua dej biopsy tuaj yeem ua qhov ntsuas ntsuas hauv cov neeg mob qog noj ntshav siab.HCC ntawm keeb kwm ntawm kev kho mob.
Tam sim no, cov kev siv los kuaj ctDNA tuaj yeem muab faib ua hom phiaj thiab tsis yog hom phiaj.Luv luv, txoj kev tsom xam xws li digital polymerase saw cov tshuaj tiv thaiv (dPCR), BEAMing digital PCR, Amplification Refractory Mutation System-PCR, Capp-Seq thiab Tam-Seq yog cov rhiab heev rau cov noob caj noob ces.Off-target txoj kev xws li tag nrho genome sequencing thiab NGS muab kev pom zoo ntawm tag nrho cov genomic toj roob hauv pes.44 Piv rau lub hom phiaj panels, tag nrho cov genome sequencing tuaj yeem ntes tsis tau tsuas yog taw tes hloov pauv thiab ntxig, tab sis kuj rov kho dua thiab luam cov lej hloov pauv.Kev kwv yees, thiab CTC thiab cfDNA yog cov cim zoo uas tuaj yeem siv rau kev saib xyuas zoo ntawm HCC.45 Tsis tas li ntawd, kev tshuaj xyuas cfDNA yuav muaj txiaj ntsig zoo hauv kev kuaj HCC.Yan et al.tau pom tias cfDNA hauv cov ntshav ntawm cov neeg mob HCC tau nce ntau dua li cov neeg mob uas muaj daim siab fibrosis thiab tswj kev noj qab haus huv.Piv rau AFP, ctDNA xav tias yuav yog qhov kev tshuaj ntsuam xyuas zoo dua rau HCC thaum ntxov.46 Hauv kev tshawb nrhiav yav tom ntej ntawm 47 kua biopsies uas kuaj cfDNA thiab cov protein nyob hauv cov pejxeem, lawv tau pom tias muaj txiaj ntsig zoo hauv kev sib txawv ntawm cov neeg mob HCC los ntawm cov neeg mob uas tsis muaj HCC.Hauv kev soj ntsuam ntawm 331 ultrasound ib txwm thiab AFP-tsis zoo cov neeg mob, qhov rhiab heev thiab qhov tshwj xeeb ntawm cfDNA rau kev kuaj HCC yog 100% thiab 94%, feem, yog li cDNA tuaj yeem kuaj HCC hauv asymptomatic HBsAg seropositive cov neeg.Hauv txoj kev tshawb fawb Yeo48, qhov ntau zaus (92.5%) ntawm hypermethylation ntawm RASSF1A txhawb nqa tau pom hauv cov neeg mob HCC.Tsis tas li ntawd, Xu et al.tsim cov qauv kuaj mob los kwv yees HCC siv lub vaj huam sib luag ntawm cov cim methylation tshwj xeeb nrog qhov tshwj xeeb thiab rhiab heev ntawm 90.5% thiab 83.3%, feem.Lub vaj huam sib luag tso cai rau cov neeg mob nrog HCC kom paub qhov txawv ntawm cov neeg mob uas muaj lwm yam kab mob siab, uas zoo dua li AFP.Lawv kuj pom tias cov kev tswj hwm ib txwm muaj uas tau kuaj pom zoo yuav muaj feem cuam tshuam rau HCC, xws li HBV kab mob lossis keeb kwm ntawm kev haus cawv.25 Peb xav tias qhov muaj feem pheej hmoo siab rau HCC tuaj yeem txhawb nqa hypermethylation ntawm cfDNA, uas tom qab ntawd ua rau muaj kev vam meej ntawm HCC, thiab yog li cfDNA tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev tshuaj xyuas cov pab pawg muaj kev pheej hmoo siab.Cai et al.Qhia tag nrho cov kev hloov pauv ntawm ctDNA thiab muab lub tswv yim zoo rau kev soj ntsuam cov qog nqaij hlav hauv cov neeg mob.49 Lub tswv yim no tuaj yeem txheeb xyuas cov qog nqaij hlav hauv nruab nrab ntawm 4.6 lub hlis ua ntej kev hloov pauv thiab tau pom tias muaj kev kuaj mob zoo dua piv rau cov ntshav biomarkers AFP, AFP-L3, thiab PIVKA-II.Qhov kev kuaj xyuas tus nqi ntawm cDNA kuaj tau pom thaum tsis muaj kev ntsuas duab, yog li kev kuaj cDNA yog qhov muaj txiaj ntsig hauv kev kuaj mob ntawm HCC thaum ntxov hauv pab pawg muaj kev pheej hmoo siab.Tsis ntev los no, cov kws tshawb fawb tau siv NGS thev naus laus zis los txheeb xyuas cov cim ntawm ntau yam kev hloov pauv caj ces (xws li 5-hydroxymethylcytosine, 5'-motif, fragmentation, nucleosome trace, HIFI) hauv 3204 cov qauv kuaj mob thiab cfDNA.50 Re-validated HIFI cov qauv nrog peb lub tsheb ciav hlau ywj pheej, kev xeem, thiab kev xeem cov teeb pom kev ruaj khov thiab txhim khu kev qha kev ntxub ntxaug ntawm HCC thiab cov neeg tsis yog HCC nrog 95.79% thiab 95.42% rhiab heev hauv HCC cov kev xeem thiab cov ntawv xeem, feem.Cov poj niam yog 95.00% thiab 97.83%, feem.Tus nqi kuaj mob ntawm HIFI txoj kev yog siab dua li ntawm AFP hauv kev paub qhov txawv HCC los ntawm cirrhosis.Tsis tas li ntawd, ctDNA kuj tseem siv rau hauv kev kho mob phais.Atsushi et al.tau txiav txim siab txog qib preoperative serum ntawm ctDNA nyob rau hauv cov neeg mob nrog HCC thiab pom tau hais tias tus nqi rov qab thiab cov extrahepatic metastasis tus nqi nyob rau hauv cov pab pawg neeg zoo cDNA yog ho ntau dua nyob rau hauv cov pab pawg neeg cDNA tsis zoo, thiab cDNA theem kuj muaj correlated.nrog qog nqaij hlav.51 Ua ib qho biomarker rhiab heev, ctDNA tuaj yeem kwv yees lub peev xwm ntawm HCC los txeeb cov hlab ntsha.Wang et al.ua tag nrho genome sequencing ntawm 46 tus neeg mob nrog HCC, thiab kev tshuaj ntsuam ntau yam qhia tau hais tias tus nqi pib ntawm allele zaus ntawm cDNA variant rau ntxeem tau rau hauv microvessels yog 0.83%, rhiab heev 89.7% thiab tshwj xeeb 80.0%.ib qho kev pheej hmoo ywj pheej rau microvascular ntxeem tau hauv HCC resectable, qhia tias cDNA tuaj yeem pab qhia kev kho kom zoo.Hauv kev xaus, ctDNA muaj feem cuam tshuam rau qhov tshwm sim thiab kev loj hlob ntawm HCC thiab tuaj yeem siv rau kev tshuaj ntsuam ntxov, kev soj ntsuam kev phais, thiab kev saib xyuas kab mob.
CTCs yog cov kab mob malignant muab tau los ntawm cov qog nqaij hlav loj lossis cov kab mob metastases uas metastasize rau cov hlab ntsha.Cov qog hlwb secrete matrix metalloproteinases (MMPs), uas ua rau hauv qab daus daim nyias nyias, tso cai rau cov qog hlwb ncaj qha nkag mus rau cov ntshav thiab cov hlab ntsha.Txawm li cas los xij, feem ntau CTCs raug tshem tawm sai sai los ntawm anoikis, tiv thaiv kab mob, lossis kev ntxhov siab.53 Txoj kev hloov pauv ntawm epithelial-mesenchymal (EMT) tso cai rau CTCs tau yooj yim cais tawm ntawm cov qog nqaij hlav hauv lub cev, cuam tshuam cov hlab ntsha, thiab tau txais kev ciaj sia, metastasis, invasiveness, thiab tshuaj tiv thaiv.Cov kev tshawb fawb tau pom tias muaj qhov sib txawv heev ntawm cov qog hlwb hauv cov qog metastatic thawj zaug.Yog li, CTC tsom xam tuaj yeem ua rau muaj kev nkag siab zoo ntawm cov qog cell heterogeneity.54
Cov cim tshwj xeeb rau HCC-koom nrog CTCs suav nrog glypican-3 (GPC3), asialoglycoprotein receptor (ASGPR), epithelial cell adhesion molecule (EpCAM) thiab qia cell-associated markers xws li CD44, CD90, 55 thiab intercellular adhesion (Molecule 11).) .56 GPC3 marker yog cell membrane-anchored protein uas tau kho mob siv rau kev soj ntsuam pathological thiab tus yam ntxwv ntawm HCC.57 Kev nthuav qhia ntawm GPC3 muaj ntau dua nyob rau hauv HCC qog hlwb nrog kev sib txawv nruab nrab thiab qis thiab txhawb nqa kev tsiv teb tsaws extrahepatic;Tsis tas li ntawd, muaj GPC3+ CTCs qhia tias metastatic HCC.58 ASGPR yog ib qho transmembrane protein uas qhia tsuas yog nyob rau saum npoo ntawm hepatocytes thiab yog heev qhia nyob rau hauv zoo-differentiated HCC.EpCAM yog ib qho ntawm feem ntau siv cov kua nplaum uas txuam nrog rau kev ntes CTCs.EpCAM tau raug txheeb xyuas tias yog tus cim saum npoo ntawm HCC cov hlwb nrog cov kab mob qia cell, 59 uas cuam tshuam nrog ntau yam kev kho mob ntawm HCC, xws li vascular invasion, soj ntsuam AFP qib, thiab qib siab ntawm mob qog noj ntshav hauv tsev kho mob Barcelona (BCLC).60 CTC EMT phenotype yog metastatic heev.54 EMT cov txheej txheem hauv CTC txhawb HCC metastasis.Kev nthuav qhia ntawm EMT cov cim xws li vimentin, twist, E-box zinc ntiv tes khi (ZEB) 1, ZEB2, qwj, slug, thiab E-cadherin tau kawm hauv daim siab CTCs los ntawm cov neeg mob HCC.58 CanPatrol ™ system tsim los ntawm Cheng [61] cais CTCs rau hauv peb pawg phenotypic raws li cov cim qhia feem ntau: epithelial phenotype (EpCAM, CK8/18/19), mesenchymal phenotype (vimentin, coiled), thiab sib xyaw phenotypes.Hauv 176 tus neeg mob, tag nrho CTC zoo dua rau AFP hauv kev sib txawv HCC los ntawm kab mob siab zoo.AUC qhov tseem ceeb rau tag nrho CTC, AFP, thiab tag nrho CTC thiab AFP yog 0.774 (95% CI, 0.704–0.834), 0.669 (95% CI, 0.587–0.750), thiab 0.821 (95% CI, 0.856). ).), raws.CTC kev faib tawm raws li EMT tuaj yeem kwv yees HCC kuaj mob, rov tshwm sim ntxov, metastasis, thiab lub sijhawm luv dua.
Tam sim no, txoj hauv kev los kuaj CSCs suav nrog cov txheej txheem lub cev thiab cov txheej txheem lom neeg.Lub cev txoj kev, feem ntau hu ua enrichment raws li biophysical zog, feem ntau yog nyob ntawm seb lub cev lub cev ntawm CSC, xws li loj, ceev, nqi, txav mus los thiab deformability.Nyob ntawm seb lub cev muaj zog, muaj ntau txoj hauv kev xws li kev pom raws li cov tshuab, dielectrophoresis, thiab lwm yam. Cov tom kawg, tseem hu ua immunoaffinity-based enrichment, feem ntau yog raws li antigen-antibody khi vim txoj kev siv cov tshuaj tiv thaiv qog nqaij hlav tshwj xeeb biomarkers. xws li EpCAM, ASGPR, human epidermal growth factor receptor 2 (HER2), prostate specific antigen (PSA), human pancytokeratin (P-CK) thiab carbamoyl phosphate synthase 1 (CPS1).62 Lwm hom, hu ua txoj kev tsis muaj txiaj ntsig, siv cov cytometry ntws los sib txawv CTCs los ntawm leukocytes raws li qhov siab dua nuclear-rau-cytoplasmic piv thiab loj.Tam sim no, tsuas yog FDA pom zoo kuaj rau kev kuaj pom ntawm CTCs yog Cell-Search ™ system, uas siv EpCAM cell nto marker. Txawm li cas los xij, kev sib xyaw cov cim raws li CTC kev kuaj pom tuaj yeem nce qhov txiaj ntsig zoo.54 Kev sib xyaw ntawm cov tshuaj tiv thaiv kab mob tiv thaiv ASGPR thiab CPS1 tau ua tiav qhov kev kuaj pom CTC ntawm 91% hauv cov neeg mob HCC.63 Zhang thiab al siv CTC-Chip nrog cov tshuaj tiv thaiv ASGPR, P. -CK thiab CPS1, thiab sib txawv HCC cov neeg mob los ntawm cov neeg mob siab mob siab lossis mob qog noj ntshav tsis yog HCC ntawm tus nqi ntawm 100%.64 Kev tshawb fawb los ntawm Wang tau kuaj pom EpCAM + CTCs hauv 60% ntawm 42 HCC cov neeg mob thiab pom muaj kev sib raug zoo ntawm ob qho tib si zoo. tus nqi thiab tus naj npawb ntawm CTCs nrog TNM theem.65 Guo li al pom tias qhov CTC-derived PCR qhab nia tau nce siab hauv 125/171 (73%) cov neeg mob uas nws qib AFP yog <20 ng / mL nrog rhiab heev ntawm 72.5% thiab a Qhov tshwj xeeb ntawm 95.0%, piv nrog 57.0% thiab 90.0% rau AFP ntawm kev txiav tawm 20 ng/mL.66 Kev sib xyaw ntawm AFP thiab CTCs tuaj yeem txhim kho HCC nrhiav pom.45 Nws ntseeg tau tias CTCs muaj qhov zoo dua AFP hauv kev tshuaj xyuas ntxov ntawm pab pawg. ntawm kev pheej hmoo siab rau HCC. Txawm li cas los xij, kev sib xyaw cov cim raws li CTC kev kuaj pom tuaj yeem nce qhov txiaj ntsig zoo.54 Kev sib xyaw ntawm cov tshuaj tiv thaiv kab mob tiv thaiv ASGPR thiab CPS1 tau ua tiav qhov kev kuaj pom CTC ntawm 91% hauv cov neeg mob HCC.63 Zhang thiab al siv CTC-Chip nrog cov tshuaj tiv thaiv ASGPR, P. -CK thiab CPS1, thiab sib txawv HCC cov neeg mob los ntawm cov neeg mob siab mob siab lossis mob qog noj ntshav tsis yog HCC ntawm tus nqi ntawm 100%.64 Kev tshawb fawb los ntawm Wang tau kuaj pom EpCAM + CTCs hauv 60% ntawm 42 HCC cov neeg mob thiab pom muaj kev sib raug zoo ntawm ob qho tib si zoo. tus nqi thiab tus naj npawb ntawm CTCs nrog TNM theem.65 Guo li al pom tias qhov CTC-derived PCR qhab nia tau nce siab hauv 125/171 (73%) cov neeg mob uas nws qib AFP yog <20 ng / mL nrog rhiab heev ntawm 72.5% thiab a Qhov tshwj xeeb ntawm 95.0%, piv nrog 57.0% thiab 90.0% rau AFP ntawm kev txiav tawm 20 ng/mL.66 Kev sib xyaw ntawm AFP thiab CTCs tuaj yeem txhim kho HCC nrhiav pom.45 Nws ntseeg tau tias CTCs muaj qhov zoo dua AFP hauv kev tshuaj xyuas ntxov ntawm pab pawg. muaj kev pheej hmoo siab rau HCC.Txawm li cas los xij, kev sib xyaw ua ke ntawm kev tshawb nrhiav CTCs tuaj yeem nce qhov feem pua ​​​​ntawm cov txiaj ntsig zoo.54 Kev sib xyaw ntawm cov tshuaj tiv thaiv ASGPR thiab CPS1 cov tshuaj tiv thaiv tau ua tiav qhov kev kuaj pom CTC ntawm 91% hauv cov neeg mob HCC.63 Zhang li al.siv CTC-Chip nrog cov tshuaj tiv thaiv kab mob tiv thaiv ASGPR, P-CK thiab CPS1, thiab tseem cais cov neeg mob nrog HCC los ntawm cov neeg muaj kab mob siab zoo lossis tsis yog HCC ntawm tus nqi ntawm 100%.частота и количество ЦОК со стадией TNM.65 Guo и соавторы обнаружили, что показатель ПЦР, полученный из ЦОК, был повышен у 125/171 (73%) пациентов, у которых уровень АФП был <20 нг/мл с чувствительностью 72,5% и специфичность 95,0% по сравнению с 57,0% и 90,0% для АФП при пороговом уровне 20 нг/мл.66 Комбинация АФП и ЦОК может улучшить обнаружение ГЦК.45 Считается, что ЦОК имеют преимущество перед АФП при раннем скрининге gv pab. zaus thiab tus naj npawb ntawm CTCs nrog TNM theem.65 Guo li al pom tias PCR muab los ntawm CTCs tau nce siab hauv 125/171 (73%) cov neeg mob uas muaj AFP qib <20 ng/mL nrog rhiab heev ntawm 72.5% thiab qhov tshwj xeeb ntawm 95.0% piv rau 57.0% thiab 90.0% rau AFP ntawm qhov kev txiav tawm ntawm 20 ng / mL.66 Kev sib xyaw ntawm AFP thiab CTCs tuaj yeem txhim kho kev tshawb pom ntawm HCC.45 CTCs raug suav tias muaj qhov zoo dua AFP hauv kev tshuaj ntsuam ntxov. pab pawg.nrog kev pheej hmoo siab ntawm HCC.Txawm li cas los xij, kev sib koom ua ke ntawm cov cim ntawm CTCs tuaj yeem nce feem pua ​​​​ntawm cov txiaj ntsig zoo.54 Ib qho sib xyaw ntawm cov tshuaj tiv thaiv ASGPR thiab CPS1 cov tshuaj tiv thaiv tau ua tiav 91% CTC kuaj pom tus nqi hauv cov neeg mob HCC.63 Zhang et al.siv CTC chips nrog cov tshuaj tiv thaiv ASGPR, P-CK thiab CPS1 thiab cov neeg mob sib txawv nrog HCC los ntawm cov kab mob siab zoo thiab tsis-HCC nrog 100%.64 Wang txoj kev tshawb fawb tau txheeb xyuas 60% ntawm EpCAM + CTCs hauv 42 HCC cov neeg mob thiab pom muaj kev cuam tshuam tseem ceeb ntawm qhov tshwm sim thiab tus naj npawb ntawm CTCs ntawm TNM theem. 65 Guo 等人发现，在AFP 在水平 <20 ng/mL 的125/171 (73%) 名患者中，CTC 衍生的PCR 评分升高，數5患者中，CTC 衍生的PCR 评分升高，數5患者中。 20 ng/mL 时的特异性为57.0% thiab 90.0%. 65 Go 等 人 人 发现 在 在 在 在 在 在 在 水平 水平 <20 的171 (73%) 名 为 为,, CTC 为 为 72.5%, Afp 在在 截止截止 截止截止Koj puas tau 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止截止 截止截止 截止截止 截止截止截止值 截止截止值截止值 截止截止值截止值 截止截止值截止值截止值截止值截止值截止值截止值为为为为为为为为为为为为为为为为) / ml 特异性 特异性的 为 为 5.0% 和 90.0%.65 Guo et al.обнаружили, что у 125/171 (73%) пациентов с уровнем АФП <20 нг/мл показатели ПЦР, полученные с помощью ЦОК, были повышены с чувствительностью 72,5% и специфичностью 95,0%, в то время как АФП на уровне отсечки Специфичность составляла 20 нг/мл. pom tias nyob rau hauv 125/171 (73%) cov neeg mob uas muaj AFP qib <20 ng/mL, CTC-derived PCR qhov tseem ceeb tau nce nrog rhiab heev ntawm 72.5% thiab qhov tshwj xeeb ntawm 95.0%, thaum AFP tau txiav txim siab tshwj xeeb. yog 20 ng / ml.ml yog 57.0% thiab 90.0%.66 Kev sib xyaw ntawm ORP thiab CTC txhim kho kev tshawb pom ntawm HCC.45 CTCs tau xav tias yuav zoo dua rau AFP hauv kev tshuaj ntsuam ntxov ntawm HCC cov neeg muaj kev pheej hmoo siab.Yog li, rau cov pab pawg CTC-zoo thiab muaj kev pheej hmoo siab HCC, CTC kuaj yuav tsum niaj hnub ua ke nrog ultrasound thiab AFP nrhiav pom.Txawm li cas los xij, CTCs yog suav tias yog qhov tseem ceeb ntawm kev kwv yees ntawm cov qog nqaij hlav metastasis thiab rov tshwm sim, thiab kev tshawb pom ntawm CTCs tsis pom zoo los ntawm tus kheej raws li cov cuab yeej kuaj mob.62 Yog li ntawd, CTC tej zaum yuav ua hauj lwm raws li ib tug zoo kwv yees biomarker dua lwm yam uas siv tam sim no. Zhou et al pom tias cov neeg mob uas muaj tus lej siab ntawm EpCAM + CTCs thiab kev tswj hwm T hlwb pom tias muaj kev pheej hmoo siab dua ntawm kev tsim HCC rov qab, dua li cov neeg uas muaj CTCs tsawg, nrog qhov rov ua dua ntawm 66.7% vs 10.3% (P <0.001).67. Ib txoj kev tshawb fawb zoo sib xws tau tshaj tawm los ntawm Zhong et al.68 Tsis tas li ntawd, Qi pom tias 101 ntawm 112 tus neeg mob (90.81%) nrog HCC, suav nrog cov neeg mob thaum ntxov, tau zoo rau CTCs thiab qhov me me HCC nodules tau kuaj pom tom qab 3. mus rau 5 lub hlis tom qab. Zhou et al pom tias cov neeg mob uas muaj tus lej siab ntawm EpCAM + CTCs thiab kev tswj hwm T hlwb tau pom tias muaj kev pheej hmoo siab dua ntawm kev tsim HCC rov qab dua li cov neeg uas tsis tshua muaj CTCs, nrog qhov sib piv ntawm 66.7% vs 10.3% (P <0.001).67 A. Cov kev tshawb fawb zoo sib xws tau tshaj tawm los ntawm Zhong et al.68 Tsis tas li ntawd, Qi pom tias 101 ntawm 112 tus neeg mob (90.81%) nrog HCC, suav nrog cov neeg mob thaum ntxov, tau zoo rau CTCs thiab qhov me me HCC nodules tau kuaj pom tom qab 3 mus rau 5 lub hlis tom qab. Чжоу thiab др.обнаружили, что у пациентов с повышенным количеством ЦОК EpCAM+ и регуляторных Т-клеток риск развития рецидива ГЦК был выше, чем у пациентов с низким количеством ЦОК, с коэффициентом рецидивов 66,7% против 10,3% (P <0,001)67. Zhou et al pom tias cov neeg mob siab EpCAM + CTCs thiab tswj T hlwb muaj kev pheej hmoo siab dua HCC dua li cov neeg uas tsis tshua muaj CTCs, nrog tus nqi rov qab ntawm 66.7% vs 10.3% (P<0.001 )67.Ib txoj kev tshawb fawb zoo sib xws tau ua los ntawm Zhong et al.68. Tsis tas li ntawd, Qi pom tias 101 ntawm 112 tus neeg mob (90.81%) nrog HCC, suav nrog cov neeg mob ntxov, muaj CTCs, thiab cov HCC nodules me me tau kuaj pom tom qab 3 mus rau 5 lub hlis ntawm kev soj ntsuam. Zhou 等 发现 发现 发现 发现 发现 发现 较数量 较数量 较 较数量 较 较 较 较 较 相比 相比 相比 相比 调节性 的 升高 的和 升高 数量 升高 升高 数量 升高 的 升高 的 的 的 的 的 高 高 高 高 高 高 高 高 高, 和 为 66.7% 和 10.3% (p <0.001). Zhou 等 人 发现 与 与 ctc 数量 少 的 患者 相比 ， epcam+ ctc 和 t 细胞 数量 的 患者 发生 hcc 复发 风险 更 ， 复发率 分别 为 为 为 为 为 为 为 为 为 为 为 为 为 为 为 为 10.3% ( p <0.001) . . . . . . . . . . . . . . . . . Чжоу thiab др.обнаружили, что пациенты с повышенным количеством ЦОК EpCAM+ и регуляторных Т-клеток имели более высокий риск рецидива ГЦК по сравнению с пациентами с меньшим количеством ЦОК, с частотой рецидивов 66,7% и 10,3% соответственно (P <0,001). Zhou et al.pom tias cov neeg mob siab EpCAM + CTCs thiab tswj T hlwb muaj kev pheej hmoo siab dua ntawm HCC dua piv rau cov neeg mob uas muaj CTCs tsawg dua, nrog rau kev rov ua dua ntawm 66.7% thiab 10.3%, feem (P <0.001).Ib txoj kev tshawb fawb zoo sib xws tau tshaj tawm los ntawm Zhong et al.68 Tsis tas li ntawd, Qi pom tias 101 ntawm 112 tus neeg mob HCC (90.81%), suav nrog cov neeg mob thaum ntxov, muaj cov txiaj ntsig CTC zoo thiab pom HCC nodules me me tom qab 3 mus ntsib.Kev soj ntsuam mus txog 5 lub hlis.Lawv kuj pom CTCs hauv 12 tus neeg mob uas muaj tus kab mob HBV ntev thiab pom cov qog HCC me me hauv 5 lub hlis hauv 2 tus neeg mob CTC zoo.69 Yog li, CTCs tuaj yeem siv los kwv yees HCC, 70 tab sis lawv tuaj yeem siv tau ntau zaus raws li kev kwv yees biomarkers.
Zoo li cfDNA, cfRNA tso tawm rau hauv cov hlab ntsha los ntawm ntau lub tshuab.Cov molecules nyob rau hauv cov ntshav peripheral sawv cev rau cov qog nqaij hlav cancer ntawm keeb kwm.Piv nrog rau cov cim uas tau pom los ntawm cov txheej txheem uas tsis yog-invasive, cfRNAs muaj ntau dua dynamically tswj, cov ntaub so ntswg tshwj xeeb, thiab ntau nyob rau hauv ib puag ncig extracellular.Qhov tseem ceeb thiab tus nqi kuaj mob ntawm 71 miRNAs (miRNAs) hauv HCC tau tshaj tawm hauv ntau qhov kev tshawb fawb.miRNAs yog endogenous non-coding RNAs (ncRNAs) uas tswj ntau yam molecular biological kev ua ub no los ntawm inhibiting kev txhais lus ntawm lub hom phiaj tub txib RNAs (mRNAs).miRNAs nyob rau hauv lub cev apoptotic encapsulated nyob rau hauv exosomes, tab sis lawv kuj muaj peev xwm ruaj khov khi rau cov ntshav cov protein thiab lipids hauv cov ntshav peripheral thiab tuaj yeem siv los ntsuas HCC.microRNAs koom nrog hauv daim siab rov tsim dua tshiab, lipid metabolism, apoptosis, o, thiab txhim kho HCC.72 Oncogenic miRNAs xws li miR-21, miR-155 thiab miR-221 paub zoo hauv HCC.Hauv particular, miR-21 plays lub luag haujlwm tseem ceeb hauv collagen synthesis nyob rau hauv extracellular matrix thiab fibrosis thiab txhawb hepatocarcinogenesis los ntawm activating hematopoietic qia hlwb.72,73 Tumor suppressor miRNAs hauv HCC suav nrog miRNA-122, miRNA-29, Let-7 tsev neeg, thiab tsev neeg miRNA-15.Cov tsev neeg Let-7 muaj ntau yam qog nqaij hlav qog miRNAs uas tsom rau RAS tsev neeg.Cov tsev neeg miR-15 suav nrog miR-15a, miR-15b, miR-16, miR-195, thiab miR-497, uas muaj cov kab sib txuas ntxiv rau qee qhov mRNAs.Tsis tas li ntawd, ntev tsis-coding RNAs (lncRNAs) thiab ncig RNAs (cirRNAs) kuj tseem ceeb rau kev tshuaj xyuas ntxov ntawm HCC.lncRNAs sawv cev rau cov chav kawm dav tshaj plaws ntawm ncRNAs, suav nrog mRNA zoo li ncRNAs, thiab koom nrog hauv kev tsim cov kab mob ntawm ntau tus tib neeg.LncRNAs ua lub luag haujlwm tswj hwm hauv lub siab microenvironment thiab kab mob siab ntev.74 CircRNAs kuj yog ib chav kawm ntawm ncRNAs nrog ntau lub luag haujlwm hauv kev tswj hwm ntawm noob caj noob ces.Tsis ntev los no, circRNAs tau raug suav tias yog cov cuab yeej kuaj mob rau HCC.
Circulating dawb RNA muaj kev ruaj ntseg zoo kawg li, nrog rau qhov kub thiab txias, pH, thiab RNase, uas ua rau kev sib cais ntawm fnRNA los ntawm cov ntshav peripheral tsawg tedious siv tus qauv RNA purification txoj kev.Cov kev siv feem ntau suav nrog NGS, microarray thiab RT-qPCR.NGS tso cai rau microRNAs ntsuas thoob plaws hauv genome.Txawm li cas los xij, txoj kev no kim heev thiab kev tsom xam tsis yog tus qauv.Nyob rau hauv sib piv, RT-qPCR yog pheej yig, sai amplifies nucleic acids, thiab muaj ntau yam zoo xws li rhiab heev, muaj tseeb dua, dav dynamic ntau yam, thiab yuav tsum tau tsawg tus qauv.Microarrays yog lwm txoj hauv kev siv rau kev kuaj miRNA raws li qhov kev xav tau thiab tshwj xeeb hybridization ntawm lub hom phiaj miRNAs nrog ntxiv DNA sojntsuam, 75 tab sis kev tshuaj xyuas ntawm cov ntaub ntawv microarray yog siv sijhawm.
Circulating miR-122 thiab Let-7 tau tshaj tawm tias yuav muaj txiaj ntsig zoo hauv kev kuaj mob HCC thaum ntxov hauv cov pab pawg muaj kev pheej hmoo siab, cov cim hauv cov neeg mob uas muaj HBV-txuas nrog cov kab mob premalignant nodules thiab HCC thaum ntxov.76 Cai et al.pom tias cov tswv cuab ntawm tsev neeg Let-7 (miR-92, miR-122, miR-125b, miR-143, miR-192, miR-16, miR-126, thiab miR-199a/b) muaj kev pheej hmoo ntawm kev mob ntev. HCC nyob rau hauv cov neeg mob uas muaj kab mob siab.Cov tsev neeg Let-7 tuaj yeem ua tus neeg sawv cev zoo biomarker rau kev kwv yees kev txhim kho ntawm HCC hauv cov pab pawg muaj kev pheej hmoo siab cuam tshuam nrog cov kab mob siab C. 77 miR-122 muaj qhov ntsuas tau zoo hauv kev kuaj pom HCC thaum ntxov hauv cov neeg mob siab cirrhosis.78 Serum circulating MiR-107 kuj tau raug soj ntsuam nyob rau theem pib ntawm HCC, 79 thiab tau pom muaj peev xwm zoo hauv cov neeg muaj kev pheej hmoo siab.Zhou et al tau tshaj tawm tias lub vaj huam sib luag ntawm miRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a thiab miR-801) tuaj yeem sib txawv HCC los ntawm kab mob siab B (CHB) thiab mob cirrhosis. rhiab heev yog 79.1% thiab 75%, thiab tshwj xeeb 76.4% thiab 91.1%, feem.80 Hauv HBV ntsig txog HCC, peb pom tias qib miR150 tau txo qis dua piv rau cov neeg mob HBV ntev tsis muaj HCC (rhiab heev 79.1%, tshwj xeeb 76.5%).-224 tau nce siab hauv HCC piv nrog kev tswj hwm kev noj qab haus huv, thiab kev soj ntsuam pab pawg tau pom ntau dua hauv cov neeg mob HCC cuam tshuam nrog HBV.kab mob siab B-koom nrog cirrhosis thiab HCC cov neeg mob tau txheeb xyuas tus siRNA cais uas muaj xya qhov sib txawv ntawm siRNAs uas tuaj yeem ntes HCC hauv kev tswj sib txawv;AUC ntau yam ntawm kev tshuaj ntsuam thaum ntxov yog zoo dua li cov neeg ua haujlwm pab dawb AFP.Lawv pom tias plaub miRNAs (miR-1972, miR-193a-5p, miR-214-3p, thiab miR-365a-3p) tuaj yeem paub qhov txawv ntawm cov neeg mob HCC los ntawm cov neeg mob uas tsis muaj HCC.Tsib overexpressing miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p, thiab miR-148a-3p) yog suav hais tias muaj peev xwm HBV kab mob hauv HCC, cirrhosis, thiab CHB biomarkers, tshwj xeeb tshaj yog miR-34a-5p tej zaum yuav yog biomarkers rau daim siab cirrhosis, 85 thiab tej zaum yuav muaj peev xwm biomarkers rau kev ntsuam xyuas ntxov ntawm HCC nyob rau hauv cov neeg muaj kev pheej hmoo siab.LncRNA feem ntau kawm nyob rau hauv HCC yog heev qhib rau hauv daim siab mob cancer (HULC).Lwm cov kev tshawb fawb tau pom tias HULC ncig hauv HCC cov neeg mob tuaj yeem siv los ua tus cim kuaj mob vim tias qhov lncRNA no tau tswj hwm zoo hauv HCC cov neeg mob piv rau cov neeg noj qab haus huv.71,86 Ntawm lwm cov lnRNAs, LINC00152 yog suav tias yog qhov zoo tshaj plaws kev kuaj mob lncRNA vim nws siab AUC, rhiab heev thiab tshwj xeeb.86 Nyob rau hauv ib txoj kev tshawb no, peripheral ntshav qhia ntawm LINC00152 maj mam nce los ntawm ib txwm noj qab nyob zoo tswj rau cov neeg mob uas muaj CHB thiab cirrhosis, thiab thaum kawg yog siab tshaj nyob rau hauv HCC.Kev tshawb fawb ntawm kev qhia ntawm circSMARCA5 hauv cov ntshav ntawm cov neeg mob HCC tau pom tias muaj kev poob qis hauv kev qhia hauv HCC xws li kab mob siab rau cirrhosis thiab cov kab mob precancerous.87 Kev soj ntsuam ntawm ROC nkhaus tau lees paub qhov muaj peev xwm ntawm cov circRNAs hauv kev paub qhov txawv ntawm cov neeg mob uas muaj kab mob siab lossis mob siab ua rau mob siab los ntawm cov neeg uas muaj HCC, tshwj xeeb tshaj yog cov neeg muaj AFP qib qis dua 200 ng / mL.Tsis tas li ntawd, Zhu tau tshuaj xyuas 13,617 cyclic RNAs hauv cov qauv ntshav los ntawm cov neeg mob HBV-koom nrog HCC thiab tau lees paub tias 6 cyclic RNAs tau qhia txawv hauv HCC thiab HBV-txuas nrog cirrhosis, qhia tias cRNAs yuav muaj txiaj ntsig.Cov cim rau kev tshuaj xyuas ntxov ntawm cov pab pawg muaj kev pheej hmoo siab xws li cov neeg muaj feem cuam tshuam nrog kab mob siab, cov neeg mob sclerosis.88
Exosomes yog membrane vesicles 40-160 nm inch;Ntau lub vesicles fuse nrog lub cell membrane thiab tso tawm mus rau hauv lub extracellular matrix.Lawv muaj ntau yam khoom siv, suav nrog lipids, proteins, RNA thiab DNA, thiab ua lub luag haujlwm tseem ceeb hauv kev sib txuas lus ntawm cov hlwb, ob qho tib si HCC thiab non-HCC hlwb.89,90 Exosomes tswj kev nce qib ntawm HCC los ntawm kev ua kom cov kab mob hepatocyte fibroblasts thiab stellate hlwb, lub cev tiv thaiv kab mob, cov kab mob hepatocytes, thiab HCC hlwb.91 Nyob rau hauv cov qog microenvironment, qog hlwb tsim ib tug loj tus naj npawb ntawm exosomes uas yog nqa los ntawm cov qog nqaij hlav cancer mus rau lub hlwb tsis paub tab, uas nyob rau hauv lem muaj kev koom tes nyob rau hauv oncogenesis, degradation, thiab cellular signaling.92 Kev tshawb fawb tau pom tias exosomes tuaj yeem hloov cov oncogenes mus rau cov hlwb li qub thaum lub sijhawm ua haujlwm pathological, uas tej zaum yuav yog ib qho ntawm cov txheej txheem ntawm cov qog nqaij hlav thiab metastasis.93 Lub luag haujlwm ntawm exosomes hauv kev mob qog noj ntshav tuaj yeem ua kom muaj zog thiab tshwj xeeb rau hom mob qog noj ntshav, 89 Exosomes tuaj yeem ua haujlwm sab hauv los ntawm cov hlwb uas nyob ib sab los yog nyob deb tswj hwm ntau lub hom phiaj hauv cov neeg txais cov hlwb uas tuaj yeem koom nrog kev sib txuas lus intercellular ions thiab cellular microenvironment kev sib cuam tshuam, lawv tuaj yeem kho cellular signaling thiab metabolism.94 Cov yam ntxwv thiab kev hloov pauv hloov pauv ntawm exosome cargo molecules ncaj qha cuam tshuam cov yam ntxwv thiab kev hloov pauv hloov pauv ntawm niam txiv qog hlwb, 95 uas tseem yog lub hauv paus rau kev siv exosomes hauv kev kuaj mob thiab kev kuaj mob qog noj ntshav, nrog rau kev kwv yees tus kheej cov lus teb rau kev kho mob qog noj ntshav. ..96
Cov kev sim tshuaj niaj hnub rau kev cais thiab txheeb xyuas cov exosomes yog qhov nyuaj, ntau kauj ruam, thiab siv sijhawm, suav nrog ultracentrifugation, pom, qhov loj me tsis suav nrog chromatography, immunoaffinity purification, Western blotting, enzyme-txuas immunosorbent assay (ELISA), PCR, thiab kev ntsuam xyuas ntws.miniaturized systems thiab lab-on-a-chip platforms siv micro / nanotechnology tau dav tsim kom ceev, yooj yim hauv kev cais tawm ntawm exosomes.Nanoparticle nrhiav kev txheeb xyuas (NTA) yog ib txoj hauv kev siv dav rau kev qhia qhov loj thiab qhov siab ntawm exosomes, suav nrog cov txheej txheem xws li sib nqus nanoparticles thiab polyhydroxyalkanoates.Microfluidic thiab electrochemical txoj kev tseem tuaj yeem ntes cov exosomes sai sai hauv cov txiaj ntsig siab.
Exosomal proteins yog cov cim tseem ceeb rau kev kuaj mob HCC.Hauv kev tshawb fawb Arbelaiz, qib ntawm 98 RasGAP SH3 binding protein (G3BP) thiab polymeric immunoglobulin receptor (PIGR) tau nce siab nyob rau hauv HCC-derived exosomes, thiab kev sib xyaw ua ke ntawm ob cov proteins tau zoo dua li ntawm AFP.Hlau overload yog ib qho tseem ceeb ua rau kev txhim kho HCC.Tseng qhia tias hepcidin tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv HCC.99 Exosomes muab los ntawm sera ntawm HCC cov neeg mob muaj cov ntawv luam ntau dua ntawm hepcidin mRNA ntau dua li lawv cov neeg noj qab haus huv, qhia tias hepcidin tuaj yeem yog cov tshuaj ntsuam xyuas biomarker tshiab rau HCC.14-3-3ζ protein nyob rau hauv exosomes tsim los ntawm 100 HCC tuaj yeem txo T cell activation, proliferation, thiab sib txawv thiab tuaj yeem ua rau T cell hloov mus rau kev tswj T hlwb, ua rau T cell depletion.101 Qhov no tau txais kev txhawb nqa los ntawm ntau qhov kev tshawb fawb tshawb nrhiav qog evasion los ntawm kev tiv thaiv kab mob, 102 uas tuaj yeem ua rau HCC tumorigenesis.
Ntxiv rau qhov muaj ecRNA nyob rau hauv cov ntshav los yog cov ntshav, RNA-enriched exosomes tuaj yeem siv rau qhov tsis muaj qhov tshwm sim ntawm lub sijhawm tiag tiag hauv kev kuaj qog nqaij hlav ntxov thiab txiav txim siab cov qog evolution thiab teb rau kev kho.Cov theem ntawm exosomal miRNA-21 nyob rau hauv cov ntshav cov ntshav nyob rau hauv pawg HCC yog 2.21 npaug tshaj nyob rau hauv pawg CHB, thiab nyob rau hauv cov pab pawg neeg HCC nws yog 5.57 npaug tshaj nyob rau hauv cov neeg noj qab nyob zoo.Hauv txoj kev tshawb fawb Wang, exosomes ho nce HCC piv nrog cov neeg mob cirrhotic nrog AUC qhov tseem ceeb ntawm 0.83 (95% CI 0.74-0.93) thiab 0.94 (95% CI 0.88-1.00).104 Cov ntaub ntawv tau txais elucidated qhov kev koom tes ntawm exosomal cargo molecules tshwj xeeb hauv kev tswj hwm ntawm oncogenesis thiab HCC kev loj hlob.105 Serum qhia ntawm miR-221, miR-103, miR-181c, miR-181a, miR-93 thiab miR-26a zoo ib yam.thiab metastasis, thiab miR21 qib siab dua hauv HCC cov neeg mob ntau dua li kev tswj hwm kev noj qab haus huv thiab tseem nyob hauv cov neeg mob CHB.102 LncRNA muaj peev xwm kuaj xyuas tus nqi hauv HCC.Cov kev tshawb fawb tau pom tias cov exosomes tau los ntawm cov neeg mob HCC muaj ntau dua ntawm LINC00161, LINC000635, thiab lncRNA qhib los ntawm kev hloov pauv qhov loj hlob-β dua li cov neeg mob tsis muaj HCC, thiab cov lncRNAs no muaj kev cuam tshuam nrog TNM theem thiab cov qog nqaij hlav.110 Conigliaro et al.CD90+ exosomes tau pom los qhia txog qib siab ntawm lncRNAH19, uas ua rau muaj qhov nce vascular endothelial kev loj hlob zoo tshaj plaws (VEGF) tso tawm thiab VEGF-R1 receptor ntau lawm, yog li stimulating angiogenesis.93 CircRNAs yog lwm hom exosomal ncRNAs - qhia nyob rau hauv qis tab sis ruaj khov theem thoob plaws hom, circRNAs kuj qhia tshwj xeeb rau hom cell, hom ntaub so ntswg, theem kev loj hlob, thiab kev tswj xyuas.111 circRNAs yog kuaj biomarkers rau kev mob qog noj ntshav thaum ntxov thiab tsawg kawg nkaus.112 Kev sim tshuaj tsis ntev los no tau pom tias qhov tshwj xeeb ntawm tus neeg miRNAs hauv kev kwv yees HCC tsis zoo tagnrho.Yog li ntawd, kev tshawb nrhiav nyuaj uas siv ntau qhov kev ntsuam xyuas (xws li miR-122 thiab miR-48a ua ke nrog AFP) tuaj yeem txhim kho qhov kev txheeb xyuas ntawm HCC thaum ntxov thiab qhov sib txawv ntawm HCC los ntawm cirrhosis.100
Cov neeg mob uas muaj CHB thiab daim siab cirrhosis yog cov feem ntau muaj kev pheej hmoo siab rau kev tsim HCC.Rau cov pab pawg uas muaj kev pheej hmoo siab, ib zaug ua tiav cov lus teb virological tau ua tiav, kev soj ntsuam tus nqi zoo raws li HCC kev pheej hmoo yuav tsum tau tsim, thiab kev tshuaj xyuas ntxov yog tus yuam sij rau kev txhim kho kev kuaj mob thiab kev kho mob ntawm HCC nrog tus nqi-zoo piv2. ..Cov kev kuaj mob ntxov ntxov rau mob qog noj ntshav muaj ntau yam kev txwv: txoj kev kuaj xyuas ntxov tsis tau tsim los rau ntau hom mob qog noj ntshav, thiab kev ua raws li feem ntau yog tsawg.Piv nrog rau cov txheej txheem tshuaj ntsuam xyuas thaum ntxov, kua biopsy thev naus laus zis muaj txiaj ntsig zoo: qhov yooj yim ntawm kev kuaj, kuaj pom panrac, zoo qauv rov tsim dua tshiab, thiab cov lus teb zoo rau cov qog heterogeneity.Muab cov txiaj ntsig zoo ntawm cov txheej txheem cuam tshuam nrog cov kua dej biopsy, lawv siv hauv HCC kev tshuaj ntsuam xyuas tsis tau raug kuaj niaj hnub.Txawm hais tias muaj kev nce qib hauv kev tshawb pom tseeb ntawm qib molecular, cov kua dej biopsy yog kim heev los kuaj xyuas HCC hauv cov neeg mob lub hom phiaj, txwv tsis pub siv dav dav piv rau cov txheej txheem tshwj xeeb xws li ultrasound thiab magnetic resonance imaging.113,114 Txawm li cas los xij, ib txoj kev tshawb fawb yav dhau los tau pom tias cov kua dej biopsy tau pom tias muaj txiaj ntsig zoo nyob rau hauv cov nqe lus ntawm kev kho lub neej zoo xyoo (QALYs).115 Cov txiaj ntsig ntawm cov kua biopsy nyob rau hauv thaum ntxov carcinoma ntawm lub plab thiab nasopharynx kuj tau pom.116,117 Qhov kev pom tam sim no yog cov kua biopsy tuaj yeem ntxiv cov ntshav biomarkers thiab kuaj hluav taws xob hauv kev kuaj pom thiab kuaj mob qog.117 118 ib
Raws li cov ntaub ntawv tam sim no, cov kua dej biopsy thev naus laus zis tau pom tias muaj kev nkag siab ntau dua thiab tshwj xeeb hauv kev tshuaj ntsuam ntxov ntawm cov pab pawg uas muaj kev pheej hmoo siab rau mob qog noj ntshav.Txawm li cas los xij ntawm cov kua dej biopsy, nws tuaj yeem paub qhov txawv ntawm HCC los ntawm cov neeg muaj kev pheej hmoo siab tsis muaj HCC, qhia qhov tseem ceeb ntawm kev tshuaj ntsuam xyuas thaum ntxov vim qhov sib txawv ntawm cov neeg muaj kev pheej hmoo siab thiab noj qab haus huv yog pom tseeb.ctDNA muaj ib nrab-lub neej luv luv thiab tuaj yeem siv los kuaj HCC, yog li txhua qhov kev hloov pauv hauv cov qog los ntawm cDNA tuaj yeem muab cov pov thawj tseeb ntawm cov qog nqaij hlav, tshwj xeeb tshaj yog rau cov qog me me.Ib qib siab ntawm ctDNA qhia txog kev txhim kho thiab kev kis mob qog noj ntshav thiab yog qhov taw qhia ntxov ntawm kev loj hlob thiab rov tshwm sim.Tsis tas li ntawd, raws li cov txiaj ntsig ntawm ctDNA, cov neeg mob tuaj yeem tau txais kev kho tus kheej thiab ua raws.119 Cov chaw methylation tshwj xeeb yuav yog qhov cim zoo dua li AFP rau kev txheeb xyuas ntxov ntawm HCC thiab cirrhotic nodules.Hauv cov xwm txheej kho tau ntawm HCC, qib siab ntawm cDNA yog qhov qhia tau tias muaj kev cuam tshuam microvascular thiab rov ua haujlwm tom qab rov ua haujlwm thiab metastasis.Kev hloov pauv ntawm tus lej luam yog cuam tshuam nrog kev ciaj sia ntawm cov neeg mob HCC.Nws tuaj yeem xav tias qhov kev ntsuam xyuas cDNA tuaj yeem koom nrog hauv kev kho tag nrho ntawm HCC, thiab cDNA tuaj yeem ua qhov qhia tau zoo ntawm kev kho mob.Cov cim raws li kev hloov pauv caj ces hauv ctDNA tau txais los ntawm cov txheej txheem kho mob los kwv yees kev ua tau zoo thiab saib xyuas cov tshuaj tiv thaiv.Kev kuaj ctDNA tej zaum yuav yog cov cuab yeej ua kua biopsy zoo tshaj plaws rau kev tshuaj ntsuam thaum ntxov.CTCs kuj tseem ua lub luag haujlwm tseem ceeb hauv kev tshuaj xyuas thaum ntxov ntawm pawg HCC uas muaj kev pheej hmoo siab.Ntau yam cim ntawm HCC-txuas nrog CTCs yog qhov tseem ceeb tshwj xeeb hauv qhov pib, kev loj hlob, thiab rov tshwm sim ntawm HCC.Raws li daim nyias nyias vesicles, exosomes koom nrog hauv kev sib txuas lus intercellular, tshwj xeeb tshaj yog nyob rau hauv HCC hlwb.Circulating microRNAs nyob ruaj khov hauv cov ntshav thiab yog li yuav muaj txiaj ntsig zoo dua rau kev kuaj HCC thaum ntxov.Maj mam, exosomal proteins thiab RNA-nplua nuj exosomes tau tshawb pom, thiab lawv qhov kev kwv yees ua tau zoo rau HCC tau lees paub.Interestingly, txawv etiologies ntawm HCC kuj yuav txuam nrog cov kev hloov pauv sib txawv, yog li peb tuaj yeem xaiv cov biomarkers sib txawv rau kev tshuaj ntsuam ntxov raws li qhov sib txawv ntawm HCC.120
Txawm li cas los xij, cov txheej txheem ua kua dej biopsy tam sim no muaj lus nug txog kev ruaj ntseg thiab tsis tuaj yeem ua nws tus kheej ua ntej kuaj lossis saib xyuas HCC, tab sis tseem tuaj yeem ua tiav kev kuaj xyuas tus kheej thiab kuaj mob.121 Raws li ib daim ntawv ntawm cov kua dej biopsy, kev kuaj pom thiab kev kuaj pom ntawm ctDNA, CTC, cfRNA thiab exosome-associated AFP lossis PIVKA-II muaj cov ntawv cog lus hauv kev kuaj mob ntxov thiab kev kwv yees ntawm HCC.Txawm li cas los xij, qhov tseeb mechanism ntawm ctDNA tso rau hauv cov ntshav tseem yuav tsum tau piav qhia.Kev nthuav tawm cov khoom lom neeg lom zem ntawm ctDNA tuaj yeem pab txhawb nws txoj kev siv los ua tus cim.Qhov me me ntawm ctDNA hauv kev ncig thiab cov qauv coj ua nruj me ntsis yog cov teeb meem rau kev siv tshuaj ntsuam xyuas cDNA hauv HCC.Tsis tas li ntawd, kev hloov pauv caj ces tsis muaj cov yam ntxwv tshwj xeeb uas tso cai rau kev txheeb xyuas qhov tseeb ntawm cov carcinogens.Txij li muaj ntau yam noob caj noob ces thiab somatic sib txawv kuj tseem muaj nyob rau hauv cov ntaub so ntswg ib txwm, kev hloov caj ces raug txheeb xyuas los ntawm cov kua dej biopsy tej zaum yuav tsis muaj txiaj ntsig hauv kev tshuaj ntsuam ntxov rau HCC.122 Cov kev txwv ntawm cov hom phiaj tseem ceeb ntawm noob caj noob ces thiab biomarkers uas pab sib txawv cDNA los ntawm cov qog DNA tsis yog cov teeb meem tseem ceeb tshaj plaws hauv kev siv cDNA.tsis muaj txiaj ntsig ntawm kev nkag siab thiab cov cim tshwj xeeb rau kev tshawb pom ntawm CTCs.Tsuas yog cov hlwb siv tau nrog cov peev xwm metastatic tau pom, thiab kev pom zoo ua ke ntawm CSC enriched cov cim tsis meej.Kev rho tawm ntawm CTCs rau kab lis kev cai thiab kev ntsuam xyuas ntawm lawv cov kev hloov pauv hloov pauv kuj yog ib txoj haujlwm nyuaj.Vim muaj teeb meem nrog kev txheeb xyuas, kev cais tawm thiab kev ua kom huv ntawm exosomes, cov txheej txheem molecular tshwj xeeb tseem tsis paub meej, thiab cov kev tshawb fawb yav dhau los ntawm cov txheej txheem ntawm exosomes thiab HCC tsis tau nyob rau hauv qhov tob, thiab txoj kev miRNAs, lncRNAs, thiab cov proteins raug txheeb rau hauv exosomes. , thiab nws tsis paub meej tias exosome uptake yog ib hom txheej txheem tshwj xeeb.Kev siv cov exosomes rau kev kuaj mob thiab kho HCC tseem nyob rau theem preclinical.Qhov tsis muaj tus qauv ntawm cov txheej txheem ua kua biopsy, xws li cov raj siv los sau cov ntshav, ntim cov ntshav, coj mus kuaj thiab kuaj pom, cais tawm thiab ua kom muaj txiaj ntsig zoo, tuaj yeem txwv tsis pub lawv siv hauv kev kho mob niaj hnub vim qhov sib txawv ntawm kev coj ua thoob plaws cov chaw kho mob.Kev ua tau zoo ntawm cov kua dej biopsy hauv kev tshuaj ntsuam thaum ntxov, kev kuaj mob, kev ntsuas kev ua tau zoo, thiab kev kwv yees ntawm HCC tseem yuav tau tshawb xyuas, tshwj xeeb tshaj yog rau cov neeg muaj kev pheej hmoo siab.Liquid biopsy thev naus laus zis muaj peev xwm ua tau zoo thiab xav tias yuav siv dav hauv kev kho mob qog noj ntshav siab yav tom ntej.
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