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UDing Jingnuo, uZhao Weifeng, iSebe leZifo ezosulelayo, iYunivesithi yaseSuzhou iSibhedlele sokuqala esiBambiseneyo, iSixeko saseSuzhou, kwiPhondo laseJiangsu, i-215000 Tel.amathumba enkqubo yokugaya kunye neminyaka emi-5 yokuphila jikelele kwe-14.1%.Izigulana ezininzi ezine-HCC zifunyaniswa zikwinqanaba eliphambili, ngoko ke ukuhlolwa kwangethuba kubalulekile ukunciphisa ukubhubha kwabantu kwi-HCC.Ukongeza kwizalathi zokubona ezisetyenziswa ngokuqhelekileyo ezifana neserum alpha-fetoprotein (AFP), lens lectin-reactive alpha-fetoprotein (AFP-L3), kunye neprothrombin engaqhelekanga (vitamin K deficiency-induced protein II, PIVKA-II), ubuchule be-fluid biopsy Kuye kwaboniswa ixabiso lokuxilonga ekufumaneni i-HCC.Xa kuthelekiswa neenkqubo ezihlaselayo, i-fluid biopsy inokubona i-metabolites embi ejikelezayo.Ubuchule be-biopsy ye-Fluid bufumanisa iiseli ezijikelezayo zethumba, i-DNA ye-tumor ejikelezayo, i-RNA ejikelezayo, kunye ne-exosomes kwaye isetyenziselwa ukuhlolwa kwangaphambili, ukuxilongwa, kunye novavanyo lwe-HCC.Eli nqaku liphonononga ibhayoloji yemolekyuli kunye nokusetyenziswa kweendlela ezahlukeneyo ze-biopsy zolwelo ukwahlula ii-biomarkers ezithembisayo ezinokuthi zibe ziinketho ezisebenzayo zovavanyo lwakwangoko lwe-HCC ukuphucula ukuhlolwa kwangoko kwamaqela e-HCC asemngciphekweni omkhulu.Amagama angundoqo: ubuchule be-biopsy ye-fluid, i-hepatocellular carcinoma, iqela elinobungozi obuphezulu.
I-Hepatocellular carcinoma (HCC) lithumba elixhaphakileyo lendlela yokwetyisa, ibekwe kwindawo yesithandathu phakathi kweemeko ezintsha zamathumba ayingozi kumadoda nabasetyhini.1 Ehlabathini lonke, umhlaza wesibindi ungowesithathu unobangela wokufa komhlaza emva komhlaza wemiphunga kunye nomhlaza we-colorectal, ubalelwa kwi-8.3% yokusweleka okunxulumene nomhlaza kuzo zonke ii-neoplasms ezimbi.1 I-prognosis ye-HCC inxulumene ngokusondeleyo nenqanaba lokuxilongwa.Ezona zizathu zokusinda kakubi kwi-HCC zii-metastases ze-intrahepatic, i-portal venous tumor thrombi, kunye ne-metastases ezikude ezithintela uqhaqho, kwaye uninzi lwezi mpawu sele zikhona kwizigulane ngexesha lokuxilongwa.
Ngokusekelwe kwizikhokelo zokuxilonga kunye nonyango, imiba ephambili yomngcipheko wokuphuhlisa i-HCC yi-cirrhosis yesibindi, i-virus ye-hepatitis B engapheliyo (HBV) okanye i-virus ye-hepatitis C (HCV), isifo sesibindi esinxilisayo, kunye nesifo sesibindi esingenalo utywala (NAFLD). ).2 Ukongeza, imingcipheko ye-HCC ibandakanya ukutya okungcoliswe yi-aflatoxin, i-schistosomiasis, ezinye izizathu ze-cirrhosis, imbali yentsapho yomhlaza wesibindi, isifo seswekile, ukutyeba, ukutshaya, kunye nokulimala kwesibindi okubangelwa ngamachiza.Amaqela angama-35 kunye nama-45 eminyaka ubudala asemngciphekweni omkhulu kufuneka ahlolwe rhoqo ngugqirha.Ukuhlolwa kwangethuba sisicwangciso esibalulekileyo sonyango lwakwangoko ukuze kuphuculwe impilo yonke yezigulane ezine-HCC.
Iimpawu ze-Biomarkers ezifana ne-AFP, i-AFP-L3 kunye ne-PIVKA-II zinconywa ukuba zihlolwe kwangaphambili kwe-HCC3,4.Ubuchule be-biopsy yolwelo bubonise iziphumo ezithembisayo kuxilongo lwakwangoko kunye novavanyo lonyango.I-5,6 Inkqubela phambili ephawulekayo yenziwe kwi-HCC ye-liquid biopsy, enokuthi ibe novakalelo oluphezulu kunye neenkcukacha ezithile kunokuba zisetyenziswe ngokuqhelekileyo iimpawu ze-serum ezifana ne-AFP (Itheyibhile 1).
I-AFP yinto esetyenziswa ngokubanzi kwi-HCC kwaye ngoku yeyona nto ineenkcukacha zebhayoloji esetyenziswa ngokubanzi kuvavanyo lwangethuba, ukuxilongwa, kunye novavanyo lwesi sifo.Inqanaba le-AFP elithe gqolo lithathwa njengomngcipheko wokuqhubela phambili kwe-HCC.I-7,8 Isantya sokubona i-hepatocellular carcinoma (sHCC) iyanda ngokuphuhliswa kwe-ultrasound kunye ne-computed tomography, kwaye i-AFP ifunyenwe ingabonakali ngokukodwa ekufumaneni i-hHCC ekusebenzeni kwekliniki.Ngokwe-retrospective multicentre study9, i-AFP positive ifunyenwe kwi-46% (616/1338) yeemeko ze-HCC kunye ne-23.4% (150/641) yeemeko ze-sHCC.Ukongezelela, amanqanaba e-AFP aphakanyisiwe kwizigulane ezinezifo ezingapheliyo zesibindi kunye ne-cirrhosis.10 Ngaloo ndlela, i-AFP inesiphumo esilinganiselweyo sokuhlola i-sHCC.I-11 Ngokutsho kwe-Asia-Pacific Clinical Practice Guidelines for Hepatocellular Carcinoma, ukusetyenziswa kwe-AFP akukhuthazwa.12 Ubungqina bezonyango bubonisa ukuba i-PIVKA-II iphezulu kune-AFP kunyango lwe-HCC kwaye ukudibanisa kwe-PIVKA-II kunye ne-AFP ine ixabiso eliphezulu lokuxilonga kwi-HCC.13 Xa kuthelekiswa ne-tissue biopsy, i-fluid biopsy ibona ikakhulu i-metabolites eyayanyaniswa nethumba kulwelo lomzimba (igazi, amathe, ulwelo lwe-pleural, ulwelo lwe-cerebrospinal, okanye umchamo) kwaye ayingeneleli kangako kwizicubu.14 Ukongeza, i-biopsies yolwelo inokubonisa iimpawu ezinobungozi ezingekhoyo kwiithishu eziphambili zethumba.15 Ii-biopsies ezingamanzi azikavavanywa kunyango lwazo zonke iintlobo zamathumba, kodwa amandla azo okuxilonga kumhlaza atsala ingqalelo yee-oncologists.I-16 i-biopsy ye-Fluid inokubona iiseli ze-tumor ezijikelezayo (i-CTCs), i-tumor ejikelezayo ye-DNA (cDNA), ejikeleza i-RNA yamahhala (ecRNA), kunye ne-exosomes.Kweli nqaku, siza kuxoxa ngeempawu, indima, kunye nokusetyenziswa kweendlela ezahlukeneyo ze-biopsy yolwelo ekuhlolweni kwangoko kwamaqela e-HCC asemngciphekweni omkhulu.
I-DNA ye-Extracellular (cfDNA) kwiisampuli zegazi ezivela kubantu abanempilo yaqala ukuchazwa ngo-1948 nguMandel et al.I-17 cfDNA liqhekeza le-DNA engenaseli elimalunga ne-160–180 bp ubude, lisuka ikakhulu kwi-lymphocytes kunye neeseli ze-myeloid.I-ctDNA liqhekeza elithile le-DNA eliguqukileyo elikhutshwe ziiseli zethumba kwigazi le-peripheral, elimele ulwazi lwe-genomic yeeseli zethumba emva kweenkqubo ezithile ze-pathophysiological, kubandakanya necrosis, apoptosis, kunye nokuphuma.Umyinge we-ctDNA kwi-cfDNA iyonke iyahluka ngokubanzi ngohlobo lwethumba, kwaye amaqhekeza e-cDNA achazwa ukuba angaphantsi kwe-167 bp ubude.18 Uphononongo luka-Underhill lubonise ukuba amaqhekeza e-cfDNA amfutshane ngokubanzi kune-cfDNA eqhelekileyo.19 Xa kuthelekiswa nabantu abasempilweni, ubude obupheleleyo bamaqhekeza e-cfDNA egazini lezigulane ezinomhlaza bufutshane, ngoko ke i-cfDNA ingasetyenziswa njengesalathisi sokuhlolwa kwethumba kwangethuba.Ukutyebisa iiseti ezithile ze-cfDNA ubude beqhekeza kunokuphucula ukubonwa kwe-cDNA ehambelana namathumba aqinileyo angeyo-metastatic.Uphononongo lubonise ukuba i-ctDNA ifumaneka ngaphezulu kwe-75% ye-pancreatic pancreatic, i-colon, isinyi, isisu, isibindi, i-ovarian, ibele, i-melanoma, kunye nomhlaza wentloko kunye nentamo.20,21 Nangona kunjalo, inani le-ctDNA egazini lixhomekeke kwindawo yethumba.22 Kuphononongo olwenziwa ngu-Bettegoud, abaguli abanomhlaza we-colorectal, webele, wesibindi, wemiphunga, kunye nowedlala lobudoda bafumaniseke banamanqanaba aphezulu e-cDNA egazini labo kuneminye imihlaza.Ngokwahlukileyo koko, kwizigulane ezinomhlaza womlomo, umhlaza we-pancreatic, umhlaza wesisu, kunye ne-glioma, ukuxinwa kwe-cDNA egazini kwakungaphantsi.amashumi amabini ananye
Ngenxa yokuba i-ctDNA iqulethe ukuguqulwa kofuzo okufanayo njengeeseli zokuqala zethumba, i-cDNA inokusetyenziselwa ukufumanisa utshintsho olukhethekileyo lwethumba kunye notshintsho lwe-epigenetic, kubandakanywa i-methylation, i-hydroxymethylation, ukuhluka kwe-nucleotide enye, kunye nokwahluka kwenani lekopi.amashumi amabini anantathu
I-DNA methylation yenye yezona nguqu zixhaphakileyo ze-epigenetic ezibangela ukunyanzeliswa kofuzo.Xa kuthelekiswa neeseli eziqhelekileyo, kukho iiyantlukwano kwinqanaba elipheleleyo le-methylation ye-tumor cell genome, ngakumbi kwi-methylation ye-tumor suppressor genes, enokuthi ibonwe kwisigaba sokuqala, ebonisa ukuba utshintsho kwi-DNA methylation lunokuba luphawu lokuqala. ukufunyanwa kwe-tumorigenesis.Iigenes ze-tumor suppressor ezinxulumene ne-HCC zinokuthi zingasebenzi ngumgqugquzeli we-methylation, ngaloo ndlela ivuselela i-tumorigenesis.24 I-DNA methylation luphawu olufanelekileyo lokufunyaniswa kwangoko kwamathumba ngenxa yokucaciswa kwezicubu zayo, ukubonwa, kunye nokuzimela ngokweminyaka.Ukongezelela, i-DNA methylation ixhaphake kakhulu xa kuthelekiswa nokuguqulwa kwe-somatic kuba kukho imimandla ekujoliswe kuyo kunye neendawo ezininzi ze-CpG ezitshintshileyo kwingingqi nganye ye-genome ekujoliswe kuyo.I-25 Ukongeza kwiindawo ezininzi ze-CpG, inani elikhulu le-loci ezimeleyo ye-hypermethylated kwi-ctDNA ichongiwe kwi-DBX2, THY1, MT1M, INK4A, VIM, FBLN1, kunye ne-RGS10.26 Xu et al.Ukuthelekiswa kweesampulu ze-cfDNA ezivela kwizigulane ze-1098 ze-HCC kunye ne-835 yolawulo olunempilo yayiyimfuza ehambelana ne-HCC yafunyaniswa ukuba inxibelelana kakhulu kunye ne-plasma cDNA methylation signatures.I-25 Ngokusekelwe kuhlalutyo lwebhubhoratri, imodeli eqikelelwayo yaphuhliswa equlethe iimpawu ze-methylation ze-10 ezinovakalelo kunye neenkcukacha ze-85.7% kunye ne-94.3%, ngokulandelanayo, kwaye aba bamakishi bahambelana kakhulu ne-tumor mass, isigaba se-tumor, kunye nokuphendula kunyango.Ezi ziphumo zibonisa ukuba ukusetyenziswa kweempawu ze-cDNA methylation kunesithembiso esikhulu ekuxilongweni, ekubekweni esweni, nakwi-prognosis ye-HCC.Kwimodeli ye-methylation equkethe i-aberrantly methylated genes (APC, COX2, RASSF1A) kunye ne-miRNA enye (miR203) eboniswe nguLu et al27, uvakalelo kunye neenkcukacha zemodeli ye-27 yokuxilonga i-HBV ehambelana ne-HBV yayifaniswa.80%.Ukongezelela, imodeli inokubona i-75% yezigulane ze-HCC ezingabonakaliyo kunye nezinga le-AFP le-20 ng / mL.I-gene ye-Ras-associated domain family 1A protein (RASSF1A) iyona nto iphambili yokulandelelana kwe-DNA kwi-genome yomntu.UAraujo et al.wagqiba ekubeni i-hypermethylation yomgqugquzeli we-RASSF1A ingaba yinto ebalulekileyo ye-biomarker yokuhlolwa kwangaphambili kwe-HCC kunye nokujoliswe kuyo kwi-molecular therapy ye-epigenetic.28 Kwisifundo esinye, i-serum RASSF1A umgqugquzeli we-hypermethylation yafunyanwa kwi-73.3% yezigulane ezine-HCC.I-29 I-nucleotide e-interspersed nucleotide element 1 (LINE-1) yenye i-retrotransposition mediator esebenzayo kakhulu.I-Hypomethylation ye-LINE-1 ifunyenwe kwi-DNA ye-66.7% yeesampuli ze-serum ze-HCC kwaye yadibaniswa nokuphindaphinda kwangaphambili kunye nokusinda kakubi emva kokutshatyalaliswa okukhulu.I-29 Hypermethylation yinkqubo eqhelekileyo yofuzo edlala indima ekhethekileyo ekuphuhliseni i-cirrhosis yesibindi kunye ne-HCC.I-30 Ngokwahlukileyo, i-hydroxymethylation yinkqubo ye-demethylation eyenza ukuvuselelwa kwemfuza kunye nokubonakaliswa, kunye nokufunyanwa kwemveliso ye-5-hydroxymethylcytosine (5-hmC) kule nkqubo ingasetyenziselwa ukuchonga i-tumor.I-Methylation kunye ne-hydroxymethylation ye-cDNA idibene ne-tumorigenesis kwaye inokuba negalelo ekuhlolweni kwangaphambili kwe-HCC.Kuphononongo lwezifundo ze-2554, i-31 ye-genome-wide 5-hmCs ifunyenwe kwiisampuli ze-cfDNA, kwaye i-32 izakhi zofuzo zichongiwe ngokuthelekisa ukulandelelana kwe-5-hmC kwizigulane ze-HCC kunye namaqela anobungozi obuphezulu njengabo banezifo ezingapheliyo.Iimodeli zokuxilonga izifo zesibindi.kunye ne-cirrhosis.Le modeli yayiphezulu kune-AFP ekuhlukaniseni i-HCC kwi-non-tumor tissue.
Utshintsho kwimimandla yekhowudi lunokukhokelela ekubhalweni okungaqhelekanga, okunokukhokelela kutshintsho kulandelelwano lweprotheyini kwaye ekugqibeleni umhlaza.Ukwahluka kwe-nucleotide enye ziziphawuli ezibalulekileyo ze-genomic zokuhlolwa kwethumba kwangoko ngenxa yokuthembeka kwazo okuphezulu kwezicubu kunye nethumba eliphakamileyo kunye nokucaciswa kwezicubu.Izifundo ezininzi ezinxulumene ne-HCC zisebenzisa ulandelelwano lwesizukulwana esilandelayo (NGS) kwi-exome kunye nolandelelwano olupheleleyo lwe-genome yomhlaza zichonge imizila yeselula eguqukileyo efana ne-TP53 kunye ne-CTNNB1, kunye nezininzi ezibandakanya i-ARID1A, MLL, IRF2.Ufuzo olutsha, i-ATM, i-CDKN2A, i-FGF19, i-PIK3CA, i-RPS6KA3 kunye ne-JAK1 ibonisa amazinga okuguqula aphakathi. Uhlalutyo oluguquguqukayo lwe-gene lubonisa ukuba utshintsho kwi-chromatin remodeling, i-Wnt / β-catenin kunye ne-JAK / STAT ye-signal transduction, i-P53-cell cycle pathway, i-epigenetic modifiers, i-oxidative stress pathways, i-PI3K / AKT / MTOR indlela kunye ne-RAS / RAF / Umzila we-MAPK kinase udlala indima ebalulekileyo kwi-HCC oncogenesis.32,33 Kuphononongo apho ukuguqulwa kwe-tumor-associated kwafunyaniswa, u-Huang et al wafumanisa ukuba ukuphindaphinda kweenguqu ezinxulumene ne-tumor ezixhomekeke kwi-ctDNA yi-19.5%, kunye ne-90% ekhethekileyo. .34 Ukongezelela, izigulane eziye zafumana ukuhlaselwa kwe-vascular kwakunokwenzeka ukuba zibe nokuguqulwa kwe-ctDNA (P = 0.041) kunye nokusinda okufutshane okuphindaphindiweyo (P <0.001). Uhlalutyo oluguquguqukayo lwe-gene lubonisa ukuba utshintsho kwi-chromatin remodeling, i-Wnt / β-catenin kunye ne-JAK / STAT ye-signal transduction, i-P53-cell cycle pathway, i-epigenetic modifiers, i-oxidative stress pathways, i-PI3K / AKT / MTOR indlela kunye ne-RAS / RAF / Umzila we-MAPK kinase udlala indima ebalulekileyo kwi-HCC oncogenesis.32,33 Kuphononongo apho ukuguqulwa kwe-tumor-associated kwafunyaniswa, u-Huang et al wafumanisa ukuba ukuphindaphinda kweenguqu ezinxulumene ne-tumor ezixhomekeke kwi-ctDNA yi-19.5%, kunye ne-90% ekhethekileyo. .34 Ukongezelela, izigulane eziye zafumana ukuhlaselwa kwe-vascular kwakunokwenzeka ukuba zibe nokuguqulwa kwe-ctDNA (P = 0.041) kunye nokusinda okufutshane okuphindaphindiweyo (P <0.001).Uhlalutyo lomsebenzi wemfuza oluguqukileyo lubonisa ukuba utshintsho kwi-chromatin remodeling, i-Wnt / β-catenin kunye ne-JAK / STAT yokubonisa, indlela ye-P53 ye-cell cycle, i-epigenetic modifiers, i-oxidative stress pathways, i-PI3K / AKT / MTOR indlela, kunye ne-RAS / RAF / MAPK kinase indlela yokudlala indima ebalulekileyo kwi-HCC tumorigenesis.32,33 Kuphononongo olufumene ukuguqulwa kwe-tumor-associated, u-Huang et al.yafumanisa ukuba ukuphindaphinda kwe-ctDNA-exhomekeke kwi-tumor-associated mutations yaba yi-19.5% kunye ne-90%..34 Iimeko zexabiso, у пациентов сосудистой инвазией чаще встречались мутации цДНК (P=0,041) kunye более короткая безрецивыдиживя (1). .34 Ukongezelela, izigulane ezine-vascular invasion zineenguqu ezininzi ze-cDNA (P = 0.041) kunye nokusinda okufutshane okungenasifo (P <0.001).Uhlalutyo olusebenzayo lwezakhi zofuzo eziguqukayo zibonakalise ukulungiswa kwe-chromatin, i-Wnt / β-catenin kunye ne-JAK / STAT yokubonisa, i-P53 i-cell cycle pathway, i-epigenetic modifiers, i-oxidative stress pathway, i-PI3K / AKT / MTOR indlela, kunye ne-RAS/RAF/MAPK indlela ye-kinase idlala indima ebalulekileyo kwi-oncogenesis ye-HCC. 32,33 在 一 项 检测 到 相关 突变 的 研究 研究 中 中 中 肿瘤 肿瘤 肿瘤 相关 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 更 可能 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). 32.33 在 一 一 检测到 到 相关 突变 研究 研究 研究 相关 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的短的无复发生存期（P<0.001）32,33 Kuphononongo olufumene utshintsho olunxulumene ne-tumor, u-Huang et al.yafumanisa ukuba ukuguqulwa kwe-tumor-associated 19.5% kuxhomekeke kwi-cDNA kunye ne-90% ye-34. Ukongezelela, izigulane eziye zahlaselwa yi-vascular invasion ziyakwazi ukuphuhlisa i-cDNA.мутация (P = 0,041) kunye ne-более короткая безрецидивная выживаемость (P <0,001). ukuguqulwa (P = 0.041) kunye nokuphila okufutshane okungenasifo (P <0.001).Olunye uhlobo lomqhubi we-HCC oluqhelekileyo yi-TP53, enezinga lokuguqula elingaphezulu kwe-30%.Uphononongo lubonise ukuba ukuphindaphindwa kweenguqu ze-TP53 kwi-ctDNA egazini kunye nomchamo ukusuka kwi-5% ukuya kwi-60%.35 Uphononongo lukaJohan lubonise ukuba i-ctDNA mutation spectrum ekupheleni kwe-HCC inezinga elifanayo lokuguqulwa kwe-HCC yokuqala, kubandakanywa umgqugquzeli we-TERT (51%), i-TP53 (32%), i-CTNNB1 (17%), i-PTEN (8%), i-mutation in AXIN1 ., ARID2, KMT2D kunye ne-TSC2 (6% nganye).36 I-β-catenin (CTNNB1) i-oncogene idlala indima ebalulekileyo kwindlela yokubonisa i-Wnt.I-coactivator ye-CTNNB1 ekhutshelweyo inokukhuthaza ukubonakaliswa kofuzo, okunokukhokelela ekwandeni kweeseli, ukuvinjelwa kwe-apoptosis, kunye ne-angiogenesis.I-CTNNB1 inokusebenzisana ne-TERT ukwenza inguqu ye-hepatocyte.33 Umgqugquzeli we-TERT uhlala eguqulwa kwamanye amathumba aqinileyo.Utshintsho kwi-TERT, enye yeenguqu zokuqala zofuzo kwinguqu enobungozi ye-HCC, inokukhokelela ekubuyiseleni i-telomerase kwi-hepatocytes ye-cirrhotic kwaye inokukhuthaza ukwanda kunye nokuthintela ukuguga.Ukuguqulwa kwe-33-37 umgqugquzeli we-TERT kuye kwabikwa ukuba kwenzeke kwi-59-90% yezigulane ezine-nodules zesibindi ezikhulayo kunye ne-HCC yokuqala kwaye zihambelana nokuphila.38
Ikopi yeenguqu zenombolo (CNA) luhlobo olululo olubalulekileyo lweenguqu ze-somatic.Uphando lubonise ukuba umthwalo oxhaphakileyo kunye nogxininiso lwe-CNA sisiginitsha ye-genomic ekwaziyo ukuqikelela ukungena kwe-tumor immune kunye nokungabandakanywa kwezinye iintlobo zomhlaza.I-39 I-infiltration signaling esebenzayo, umsebenzi ophezulu we-cytolytic, ukuvuvukala okukhulu kunye neempawu zofuzo ezinxulumene nokubonakaliswa kwe-antigen kwi-HCC.Uhlalutyo lwedatha ye-polymorphisms ye-nucleotide eyodwa kwizifundo ze-477 ibonise umthwalo ophantsi kwi-CNS.Ngokwahlukileyo, izicubu ezingazinzanga ze-chromosomally ezinomthwalo ophezulu we-CNA obanzi zibonise iimpawu zokulahlwa komzimba kwaye zayanyaniswa nokwanda, ukulungiswa kwe-DNA, kunye nokungasebenzi kwe-TP53.Xu et al.ibonise ukuba iqela le-HCC linamanqaku aphezulu e-CNA kuneqela lesifo esingapheliyo sesibindi.40 Ukusebenzisa ulandelelwano lwe-genome epheleleyo yeseli enye, ii-CNAs zafunyanwa ukuba zivele kwangoko kwi-hepatocarcinogenesis kwaye zihlala zizinzile ngexesha lokunyuka kwe-tumor.41 Chung et al.ifumanise ukuba amanqanaba e-cfDNA anyuswe kakhulu kwizigulana ze-HCC kunye nokuba ii-CNAs ze-genome-wide kwi-cfDNA yayiyi-prognostic marker ebalulekileyo ezimeleyo kwizigulana ze-HCC ezinyangwa nge-sorafenib.Izigulane ze-42 ezinomthwalo ophezulu we-CNA zazinokwenzeka ukuba zibe nokuqhubela phambili kwesifo kunye nokufa kunezo ezinomthwalo ophantsi we-CNA.Ollerich et al.yafumanisa ukuba ikopi yenombolo yokungazinzi (CNI) ingasetyenziselwa ukuvavanya i-CNA kwi-cfDNA yezigulane ezinomhlaza.Baye baqaphela ukuba abaguli abanomhlaza ophezulu babenamanqaku aphezulu kakhulu e-CNI kuneqela lolawulo, elivavanya impendulo yesigulane kwi-systemic chemotherapy kunye ne-immunotherapy.43 Ezi ziphumo zibonisa ukuba ii-CNAs ezifunyenwe kwiisampulu ze-liquid biopsy zinokusebenza njengezalathi zentelekelelo kwizigulana ezinomhlaza ophezulu.HCC kwimvelaphi yonyango lwenkqubo.
Okwangoku, iindlela ezisetyenziselwa ukufumanisa i-ctDNA zinokwahlulwa zibe ziindlela ekujoliswe kuzo nezingajoliswanga.Ngokufutshane, iindlela ezijoliswe kuzo ezifana nedijithali ye-polymerase chain reaction (dPCR), i-BEAMing digital PCR, i-Amplification Refractory Mutation System-PCR, iCapp-Seq kunye ne-Tam-Seq zinovakalelo oluphezulu kwiimfuza ezichazwe kwangaphambili.Iindlela ezingezizo ekujoliswe kuzo ezifana nolandelelwano lwe-genome epheleleyo kunye ne-NGS zibonelela ngombono obanzi wayo yonke i-genomic landscape.44 Xa kuthelekiswa neepaneli ekujoliswe kuzo, ulandelelwano lwe-genome epheleleyo alukwazi ukubona kuphela ukuguqulwa kwamanqaku kunye nokufakwa, kodwa kunye nohlengahlengiso kunye nokwahluka kwamanani ekopi.I-prognosis, kunye ne-CTC kunye ne-cfDNA zizalathisi ezilungileyo ezinokusetyenziselwa ukubeka esweni okuguquguqukayo kwe-HCC.45 Ukongeza, uhlalutyo lwe-cfDNA lunokuba luncedo ngakumbi ekubhaqeni i-HCC.Yan et al.ibonise ukuba i-cfDNA kwiplasma yezigulana ezine-HCC yayiphezulu kakhulu kunezigulana ezine-fibrosis yesibindi kunye nolawulo olusempilweni.Xa kuthelekiswa ne-AFP, i-ctDNA kulindeleke ukuba ibe luphawu olungcono lokuhlola i-HCC yokuqala.46 Kuphononongo olulindelekileyo lwe-47 ye-biopsies yolwelo evavanye i-cfDNA kunye neprotheyini kuluntu lwabemi, ziboniswe zisebenza ngempumelelo ekwahluleni izigulana ezine-HCC kwizigulana ezingenayo i-HCC.Ekulandeleni i-331 ye-ultrasound eqhelekileyo kunye ne-AFP-negative izigulane, uvakalelo kunye neenkcukacha ze-cfDNA zokuxilonga i-HCC yayiyi-100% kunye ne-94%, ngokulandelanayo, ngoko ke i-cDNA inokubona i-HCC kubantu abangabonakaliyo be-HBsAg be-seropositive.Kuphononongo lwe-Yeo48, i-frequency ephezulu (92.5%) ye-hypermethylation yomgqugquzeli we-RASSF1A ifunyenwe kwizigulane ezine-HCC.Ukongeza, uXu et al.udale imodeli yokuxilonga ukuqikelela i-HCC usebenzisa iphaneli yamanqaku athile e-methylation kunye neenkcukacha kunye novakalelo lwe-90.5% kunye ne-83.3%, ngokulandelanayo.Iphaneli ivumela izigulane ezine-HCC ukuba zihluke kwizigulane ezinezinye izifo zesibindi, ezingcono kune-AFP.Baye bafumanisa ukuba ulawulo oluqhelekileyo oluye lwafunyaniswa lune-HIV lunokuba nemingcipheko ye-HCC, njengosulelo lwe-HBV okanye imbali yokusetyenziswa kotywala.25 Sicinga ukuba izinto ezinobungozi obuphezulu be-HCC zinokukhuthaza i-hypermethylation ye-cfDNA, ethi ke ibe negalelo ekuqhubeleni phambili kwe-HCC, kwaye ke i-cfDNA inokudlala indima ephambili ekuhlolweni kwamaqela asemngciphekweni omkhulu.Cai et al.shwankathela uluhlu olupheleleyo lweenguqu ze-ctDNA kwaye unikeze isicwangciso esomeleleyo sokuvavanya umthwalo wethumba kwizigulana.I-49 Esi sicwangciso sinokuchonga i-tumorigenesis i-median yeenyanga ze-4.6 ngaphambi kokuguqulwa kwemifanekiso kwaye ibonise ukusebenza okuphezulu kokuxilonga xa kuthelekiswa ne-serum biomarkers AFP, AFP-L3, kunye ne-PIVKA-II.Ixabiso lokuxilonga lovavanyo lwe-cDNA libonakaliswe xa uvavanyo lomfanekiso lungekho, ngoko uvavanyo lwe-cDNA lunexabiso ekuxilongweni kwe-HCC yokuqala kumaqela anobungozi obukhulu.Kungekudala, izazinzulu zisebenzisa iteknoloji ye-NGS ukuhlalutya izibonakaliso ze-multivariate genetic variation (kubandakanywa i-5-hydroxymethylcytosine, i-5'-motif, i-fragmentation, i-nucleosome trace, i-HIFI) kwiisampuli zekliniki ze-3204 kunye ne-cfDNA.Iimodeli ze-50 eziqinisekisiweyo kwakhona ze-HIFI ezinezitimela ezintathu ezizimeleyo, uvavanyo, kunye neeseti zokuvavanya zibonise ucalulo oluzinzile noluthembekileyo phakathi kwe-HCC kunye ne-non-HCC yabantu abane-95.79% kunye ne-95.42% yobuntununtunu kwi-HCC-specific test and test sets, ngokulandelanayo.Izini zazingama-95.00% kunye nama-97.83%, ngokulandelelanayo.Ixabiso lokuxilonga indlela ye-HIFI liphezulu kune-AFP ekwahlulahluleni i-HCC kwi-cirrhosis.Ukongeza, i-ctDNA ikwasetyenziswa kunyango lotyando.Atsushi et al.inqume amanqanaba e-serum yangaphambili ye-ctDNA kwizigulane ezine-HCC kwaye yafumanisa ukuba izinga lokuphindaphinda kunye nesantya se-extrahepatic metastasis kwiqela le-cDNA elihle laliphezulu kakhulu kuneqela elibi le-cDNA, kwaye amanqanaba e-cDNA ayedityaniswa kakhulu.ngokunyuka kwethumba.51 Ekubeni sisiphawuli sebhayoloji esinovakalelo oluphezulu, i-ctDNA inokuqikelela ukubanako kwe-HCC ukuhlasela iinqanawa.Wang et al.yenza ulandelelwano lwe-genome epheleleyo yezigulane ze-46 ezine-HCC, kunye nohlalutyo lwe-multivariate lubonise ukuba ixabiso lomgubasi we-allele frequency ye-cDNA eyahlukileyo yokuhlaselwa kwi-microvessels yi-0.83%, ubuntununtunu 89.7% kunye neenkcukacha ze-80.0%.umngcipheko ozimeleyo wokuhlaselwa kwe-microvascular kwi-HCC ehlaziyiweyo, ebonisa ukuba i-cDNA inokunceda ukukhokela unyango olufanelekileyo.Ukuqukumbela, i-ctDNA ibandakanyeka ngokupheleleyo ekwenzekeni nasekuphuhlisweni kwe-HCC kwaye ingasetyenziselwa uhlolo kwangethuba, uvavanyo lotyando, kunye nokuhlola izifo.
Ii-CTCs ziiseli ezinobungozi eziphuma kumathumba aphambili okanye i-metastases ekhula kwigazi.Iiseli ze-tumor zikhupha i-metalloproteinases ye-matrix (MMPs), eqhekeza inwebu engaphantsi, ivumela iiseli zethumba ukuba zingene ngokuthe ngqo kwigazi kunye nemithambo ye-lymph.Nangona kunjalo, ezininzi ii-CTCs zipheliswa ngokukhawuleza yi-anoikis, ukuhlaselwa kwe-immune, okanye uxinzelelo lwe-shear.53 I-epithelial-mesenchymal transition (EMT) ivumela ii-CTCs ukuba zibe zodwa ngokukhawuleza kwiithishu eziphambili zethumba, zihlasele ii-capillaries, kwaye zifumane ubomi obuphuculweyo, i-metastasis, invasiveness, kunye nokuxhatshazwa kweziyobisi.Uphononongo lubonise ukuba kukho i-heterogeneity enzulu phakathi kweeseli zethumba kwiiseli eziphambili ze-metastatic.Ke, uhlalutyo lwe-CTC lunokukhokelela ekuqondeni okubanzi kwe-tumor cell heterogeneity.54
Iimpawu ezikhethekileyo ze-CTCs ezinxulumene ne-HCC ziquka i-glypican-3 (GPC3), i-asialoglycoprotein receptor (ASGPR), i-epithelial cell adhesion molecule (EpCAM) kunye neempawu ezinxulumene ne-stem cell ezifana ne-CD44, i-CD90, i-55 kunye ne-intercellular adhesion molecule 1 (ICAM1).) .56 Isiphawuli se-GPC3 yiprotheyini ene-cell membrane-anchored esetyenziswa ngokwezonyango kuhlalutyo lwe-pathological kunye nokubonakaliswa kwe-HCC.I-57 Ukubonakaliswa kwe-GPC3 kuxhaphake kakhulu kwiiseli ze-tumor ze-HCC ezinokwahlula okuphakathi kunye nokuphantsi kwaye zikhuthaza ukufuduka kwe-extrahepatic;Ukongeza, ubukho be-GPC3 + ​​CTC bubonisa i-HCC ye-metastatic.I-58 ASGPR yiprotheni ye-transmembrane echazwe kuphela kumphezulu we-hepatocytes kwaye ibonakaliswe kakhulu kwi-HCC eyahluke kakhulu.I-EpCAM yenye yezona ziqhelekileyo zisetyenziswa kwi-membrane ehambelana neeprotheni zokubamba ii-CTCs.I-EpCAM ichongiwe njengommakishi womphezulu weeseli ze-HCC ezineempawu ze-stem cell, i-59 ehambelana neempawu ezahlukeneyo zekliniki ze-HCC, ezifana nokuhlasela kwe-vascular, amanqanaba avavanyiweyo e-AFP, kunye nenqanaba eliphezulu lomhlaza wesibindi kwiSibhedlele saseBarcelona (BCLC).I-phenotype ye-60 CTC EMT ine-metastatic kakhulu.Iinkqubo ze-54 ze-EMT kwi-CTC zikhuthaza i-HCC metastasis.Ukubonakaliswa kwamanqaku e-EMT afana ne-vimentin, i-twist, i-E-box zinc finger binding (ZEB) 1, i-ZEB2, i-snail, i-slug, kunye ne-E-cadherin ziye zafundwa kwii-CTC zesibindi ezivela kwizigulane ze-HCC.58 Inkqubo yeCanPatrol™ ephuhliswe nguCheng [61] ihlela ii-CTCs zibe ngamacandelwana amathathu e-phenotypic asekelwe kumakishi abonakaliswe kakhulu: i-epithelial phenotype (EpCAM, CK8/18/19), i-mesenchymal phenotype (vimentin, coiled), kunye ne-mixed phenotypes.Kwizigulane ze-176, i-CTC iyonke yayiphezulu kune-AFP ekuhlukaniseni i-HCC kwisifo sesibindi esinobungozi.Amaxabiso e-AUC e-CTC iyonke, i-AFP, kunye ne-CTC epheleleyo kunye ne-AFP edibeneyo yayiyi-0.774 (95% CI, 0.704-0.834), 0.669 (95% CI, 0.587-0.750), kunye ne-0.821 (95% CI, 0.886-0.886) ).), ngokulandelelanayo.Ukuhlelwa kwe-CTC esekelwe kwi-EMT inokuqikelela ukuxilongwa kwe-HCC, ukuphindaphinda kwangethuba, i-metastasis, kunye nexesha elifutshane elifutshane.
Okwangoku, iindlela zokufumana ii-CSC zibandakanya iindlela zomzimba kunye neendlela zebhayoloji.Iindlela zenyama, ezidla ngokubizwa ngokuba kukutyebisa okusekwe kwiipropathi zebhayoloji, ubukhulu becala zixhomekeke kwiimpawu ezibonakalayo ze-CSC, ezifana nobukhulu, ubuninzi, intlawulo, ukushukuma kunye nokukhubazeka.Ngokuxhomekeke kwiimpawu zomzimba, kukho iindlela ezahlukeneyo ezifana neenkqubo zokuhluza-based, i-dielectrophoresis, njl njl. Le yokugqibela, eyaziwa ngokuba yi-immunoaffinity-based enrichment, isekelwe ikakhulu kwi-antigen-antibody ebophelelayo ekubeni indlela isebenzisa izilwa-buhlungu ezichasene ne-biomarkers ye-tumor-specific. njenge-EpCAM, ASGPR, i-epidermal growth factor receptor 2 (HER2), i-prostate specific antigen (PSA), i-pancytokeratin yabantu (P-CK) kunye ne-carbamoyl phosphate synthase 1 (CPS1).62 Olunye uhlobo, olubizwa ngokuba yi-no-richment method, isebenzisa i-flow cytometry ukwahlula ii-CTCs ukusuka kwi-leukocytes ngokusekelwe kumlinganiselo ophezulu wenyukliya-to-cytoplasmic kunye nobukhulu.Okwangoku, olona vavanyo luvunyiweyo yi-FDA lokuchongwa kwee-CTC yinkqubo ye-Cell-Search™, esebenzisa i-EpCAM cell surface marker. Nangona kunjalo, ukufumanisa i-CTC edibeneyo esekelwe kumakishi kunokunyusa izinga le-positivity.54 Umxube we-antibodies ngokumelene ne-ASGPR kunye ne-CPS1 iphumelele izinga lokufumanisa i-CTC ye-91% kwizigulane ze-HCC.63 Zhang et al wasebenzisa i-CTC-Chip enee-antibodies ezichasene ne-ASGPR, P. -CK kunye ne-CPS1, kunye nezigulane ze-HCC zahlula abo banesifo sesibindi esibi okanye umhlaza ongekho we-HCC kwizinga le-100%.64 Uphononongo olwenziwa nguWang lufumene i-EpCAM + CTCs kwi-60% yezigulane ze-42 ze-HCC kwaye zifumene ukulungelelaniswa okubalulekileyo phakathi kokubini okulungileyo. izinga kunye nenani le-CTCs kunye nesigaba se-TNM.65 Guo et al wafumanisa ukuba i-PCR ephuma kwi-CTC ifunyenwe kwi-125/171 (73%) izigulane ezinezinga le-AFP <20 ng / mL nge-sensitivity ye-72.5% kunye ne- ukucaciswa kwe-95.0%, xa kuthelekiswa ne-57.0% kunye ne-90.0% ye-AFP kwi-cutoff 20 ng / mL.66 Ukuhlanganiswa kwe-AFP kunye ne-CTCs kunokuphucula ukubonwa kwe-HCC.45 Kukholelwa ukuba ii-CTC zinenzuzo ngaphezu kwe-AFP ekuhlolweni kwangaphambili kwamaqela. kumngcipheko ophezulu we-HCC. Nangona kunjalo, ukufumanisa i-CTC edibeneyo esekelwe kumakishi kunokunyusa izinga le-positivity.54 Umxube we-antibodies ngokumelene ne-ASGPR kunye ne-CPS1 iphumelele izinga lokufumanisa i-CTC ye-91% kwizigulane ze-HCC.63 Zhang et al wasebenzisa i-CTC-Chip enee-antibodies ezichasene ne-ASGPR, P. -CK kunye ne-CPS1, kunye nezigulane ze-HCC zahlula abo banesifo sesibindi esibi okanye umhlaza ongekho we-HCC kwizinga le-100%.64 Uphononongo olwenziwa nguWang lufumene i-EpCAM + CTCs kwi-60% yezigulane ze-42 ze-HCC kwaye zifumene ukulungelelaniswa okubalulekileyo phakathi kokubini okulungileyo. izinga kunye nenani le-CTCs kunye nesigaba se-TNM.65 Guo et al wafumanisa ukuba i-PCR ephuma kwi-CTC ifunyenwe kwi-125/171 (73%) izigulane ezinezinga le-AFP <20 ng / mL nge-sensitivity ye-72.5% kunye ne- ukucaciswa kwe-95.0%, xa kuthelekiswa ne-57.0% kunye ne-90.0% ye-AFP kwi-cutoff 20 ng / mL.66 Ukuhlanganiswa kwe-AFP kunye ne-CTCs kunokuphucula ukubonwa kwe-HCC.45 Kukholelwa ukuba ii-CTC zinenzuzo ngaphezu kwe-AFP ekuhlolweni kwangaphambili kwamaqela. kumngcipheko omkhulu we-HCC.Nangona kunjalo, ukubonwa okuhlanganisiweyo okusekelwe kumakishi kunokunyusa ipesenti yeziphumo ezilungileyo.54 Umxube we-anti-ASGPR kunye ne-CPS1 antibodies uzuze izinga lokufumanisa i-CTC ye-91% kwizigulane ezine-HCC.63 Zhang et al.isebenzise i-CTC-Chip enee-antibodies ezichasene ne-ASGPR, i-P-CK kunye ne-CPS1, kwaye yahlula izigulane ezine-HCC kulabo abanesifo sesibindi esinobungozi okanye i-non-HCC kwizinga le-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 групп. i-frequency kunye nenani le-CTCs kunye nesigaba se-TNM.65 UGuo et al wafumanisa ukuba i-PCR evela kwi-CTCs iphakanyisiwe kwi-125 / 171 (73%) izigulane ezinamazinga e-AFP <20 ng / mL ngovakalelo lwe-72.5% kunye neenkcukacha ezithile ze-AFP. I-95.0% xa kuthelekiswa ne-57.0% kunye ne-90.0% ye-AFP kwinqanaba lokunqunyulwa kwe-20 ng / mL.66 Ukuhlanganiswa kwe-AFP kunye ne-CTCs kunokuphucula ukubonwa kwe-HCC.45 CTCs zibhekwa njengenzuzo kwi-AFP ekuhlolweni kwangaphambili. amaqela.kunye nomngcipheko omkhulu we-HCC.Nangona kunjalo, ukuchongwa okudityanisiweyo okusekwe kumanqaku ee-CTC kunokunyusa ipesenti yeziphumo ezilungileyo.I-54 Umxube we-anti-ASGPR kunye ne-CPS1 antibodies uzuze i-91% yezinga lokufumanisa i-CTC kwizigulane ezine-HCC.63 Zhang et al.isetyenzisiwe iitshiphusi ze-CTC ezine-antibodies ezichasene ne-ASGPR, i-P-CK kunye ne-CPS1 kunye nezigulane ezikhethekileyo ezine-HCC kwisifo sesibindi esinobungozi kunye ne-non-HCC kunye ne-100%.Uphononongo luka-64 lukaWang luchonge i-60% ye-EpCAM+ CTCs kwizigulane ezingama-42 ze-HCC kwaye yafumana unxulumano olubalulekileyo phakathi kwezehlo kunye nenani le-CTCs kwinqanaba le-TNM. 65 Guo 等人发现，在AFP 水平<20 ng/mL 的125/171 (73%) 名患者中，CTC 衍生的PCR 评分升高，敏感性，敏感性，敏感性，敏感性，敏感性，敏感性，敏感性，敏感性，敏感性，A77.值為20 ng/mL 时的特异性為57.0% 和90.0%. 65 I-nuo 等 等 发现 在 在 在 <20 NG / ML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 截止 截止 截止 截止 截止 截止 截止 截止 为 为 截止值 截止 为 为 为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. bafumanisa ukuba kwi-125/171 (73%) izigulane ezinamazinga e-AFP <20 ng / mL, ixabiso le-PCR eliphuma kwi-CTC liphakanyiswe ngovakalelo lwe-72.5% kunye ne-95.0% ethile, ngelixa i-AFP yayikwi-specific-cut off. yayingama-20 ng/mL.ml yaba 57.0% kunye 90.0%.66 Indibaniselwano ye-ORP kunye ne-CTC iphucula ukubonwa kwe-HCC.Ii-CTC ze-45 zicingelwa ukuba ziphezulu kune-AFP ekuhlolweni kwangaphambili kwabantu abasengozini enkulu ye-HCC.Ngaloo ndlela, kumaqela e-CTC-positive kunye nomngcipheko ophezulu we-HCC, uvavanyo lwe-CTC kufuneka ludibaniswe rhoqo kunye ne-ultrasound kunye ne-AFP yokufumanisa.Nangona kunjalo, ii-CTC zibhekwa njengento ebalulekileyo yokuqikelela i-tumor metastasis kunye nokuphindaphinda, kwaye ukufumanisa ii-CTCs akukhuthazwa ngokuzimeleyo njengesixhobo sokuxilonga.62 Ke ngoko, i-CTC inokusebenza njenge-biomarker eqikelelwayo engcono kunabanye abamakishi abasetyenziswayo ngoku. UZhou et al wafumanisa ukuba izigulane ezinamanani aphakamileyo e-EpCAM + CTCs kunye neeseli ze-T ezilawulayo zibonise umngcipheko ophezulu wokuphuhlisa i-HCC ukuphindaphinda, kunezo ezinamanani aphantsi e-CTCs, kunye ne-recurrence ratio ye-66.7% vs 10.3% (P <0.001) .67) Uphononongo olufanayo luxelwe nguZhong et al.68 Ukongezelela, i-Qi yafumanisa ukuba i-101 yezigulane ze-112 (90.81%) ezine-HCC, kubandakanywa nezo zinesifo sokuqala, zilungile kwi-CTCs kwaye i-HCC encinci kakhulu yafunyanwa emva kwe-3. ukuya kwiinyanga ezi-5 zokulandelela. UZhou et al wafumanisa ukuba izigulane ezinamanani aphakamileyo e-EpCAM + CTCs kunye neeseli ze-T ezilawulayo zibonise umngcipheko ophezulu wokuphuhlisa i-HCC ukuphindaphinda kunezo ezinamanani aphantsi e-CTCs, kunye ne-recurrence ratio ye-66.7% vs 10.3% (P <0.001) .67 A. Uphononongo olufanayo luxelwe nguZhong et al.68 Ukongeza, i-Qi yafumanisa ukuba i-101 yezigulane ze-112 (90.81%) ezine-HCC, kubandakanywa nezo zinesifo sokuqala, zilungile kwi-CTCs kwaye i-HCC encinci kakhulu yafunyanwa emva kwe-3 ukuya. Iinyanga ezi-5 zokulandelela. Чжоу и 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. U-Zhou et al wafumanisa ukuba izigulane ezine-EpCAM + CTCs eziphakamileyo kunye neeseli ze-T ezilawulayo zinomngcipheko ophezulu wokuphindaphinda kwe-HCC kunezo zine-CTC eziphantsi, kunye nezinga lokuphindaphinda kwe-66.7% vs 10.3% (P <0.001) 67.Uphononongo olufanayo lwenziwa nguZhong et al.68. Ukongezelela, i-Qi yafumanisa ukuba i-101 kwizigulane ze-112 (90.81%) ezine-HCC, kubandakanywa nezo zinesifo sokuqala, zine-CTCs, kwaye ii-nodules ezincinci ze-HCC zifunyenwe emva kwe-3 kwiinyanga ze-5 zokulandelwa. Zhou 等 人 发现, 与 ctc 数量 数量 数量 数量 患者 患者 患者患者 患者 相比 和 和 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 复发 风险 复发 风险 风险 风险 风险 风险 高 高 高 高更, 复发率 为 为 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 и 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.ifumene ukuba izigulane ezine-EpCAM + CTCs eziphakamileyo kunye neeseli ze-T ezilawulayo zinomngcipheko ophezulu wokuphindaphinda kwe-HCC xa kuthelekiswa nezigulane ezine-CTC ezimbalwa, kunye namazinga okuphindaphinda kwe-66.7% kunye ne-10.3%, ngokulandelanayo (P <0.001).Uphononongo olufanayo luchazwe nguZhong et al.68 Ukongeza, i-Qi yafumanisa ukuba i-101 ye-112 yezigulane ze-HCC (90.81%), kubandakanywa nezigulane ezinesifo sokuqala, zineziphumo ezilungileyo ze-CTC kwaye zifumene ama-nodules amancinci kakhulu e-HCC emva kokutyelela i-3.Ukuqwalaselwa ukuya kwiinyanga ezi-5.Baye bafumana kwakhona ii-CTCs kwizigulane ezili-12 ezinosulelo olungapheliyo lwe-HBV kwaye bafumana amathumba amancinci e-HCC phakathi kweenyanga ezi-5 kwizigulane ezi-2 ze-CTC.69 Ngoko ke, ii-CTCs zingasetyenziselwa ukuqikelela i-HCC, i-70 kodwa zinokusetyenziswa njengesiqhelo njengee-biomarkers eziqikelelwayo.
Njenge-cfDNA, i-cfRNA ikhutshelwa egazini ngeendlela ezahlukeneyo.Ezi molekyuli kwigazi le-peripheral zimele izicubu ezinomhlaza wemvelaphi.Xa kuthelekiswa namanqaku afunyenwe ngeendlela ezingangeneleliyo, ii-cfRNAs zilawulwa ngamandla ngakumbi, zithe ngqo kwizicubu, kwaye zininzi kwindawo engaphandle kweseli.Ukubaluleka kunye nexabiso lokuxilongwa kwe-71 miRNAs (miRNAs) kwi-HCC kuye kwabikwa kwizifundo ezininzi.I-miRNAs zi-endogenous non-coding RNAs (ncRNAs) ezilawula imisebenzi eyahlukeneyo yebhayoloji yemolekyuli ngokuthintela ukuguqulelwa kwee-RNAs zomthunywa (mRNAs).I-miRNAs ibekwe kwimizimba ye-apoptotic efakwe kwi-exosomes, kodwa inokubophelela ngokuzinzileyo kwiiproteni ze-serum kunye ne-lipids kwigazi le-peripheral kwaye ingasetyenziselwa ukuvavanya i-HCC.I-microRNAs ibandakanyeka ekuvuseleleni isibindi, i-lipid metabolism, i-apoptosis, ukuvuvukala, kunye nokuphuhliswa kwe-HCC.72 I-Oncogenic miRNAs efana ne-miR-21, miR-155 kunye ne-miR-221 zaziwa kakhulu kwi-HCC.Ngokukodwa, i-miR-21 idlala indima ephambili kwi-collagen synthesis kwi-matrix ye-extracellular kunye ne-fibrosis kwaye ikhuthaza i-hepatocarcinogenesis ngokuvula iiseli ze-hematopoietic stem.I-72,73 i-Tumor suppressor miRNAs kwi-HCC ibandakanya i-miRNA-122, i-miRNA-29, intsapho ye-Let-7, kunye nosapho lwe-miRNA-15.Usapho lwe-Let-7 luqulathe uninzi lwe-tumor suppressor miRNAs ezijolise kusapho lwe-RAS.Intsapho ye-miR-15 ibandakanya i-miR-15a, i-miR-15b, i-miR-16, i-miR-195, kunye ne-miR-497, enolandelelwano oluhambelanayo kwiimRNA ezithile.Ukongeza, ii-RNAs ezinde ezingabhalwanga iikhowudi (lncRNAs) kunye neesetyhula zeRNA (cirRNAs) nazo zibalulekile ekuhlolweni kwangaphambili kwe-HCC.I-lncRNA imele iklasi ebanzi ye-ncRNAs, kuquka i-mRNA-efana ne-ncRNAs, kwaye ibandakanyeka kwi-pathogenesis yezifo ezininzi zabantu.I-LncRNAs idlala indima yokulawula kwi-microenvironment yesibindi kunye nesifo esingapheliyo sesibindi.I-74 CircRNAs nayo iklasi ye-ncRNAs enemisebenzi emininzi kulawulo lwe-gene expression.Kutshanje, ii-circRNAs zithathwe njengezixhobo zokuxilonga ze-HCC.
I-RNA ejikelezayo yasimahla inozinzo olumangalisayo, kubandakanya ukumelana nobushushu, i-pH, kunye ne-RNase, eyenza ukwahlukaniswa kwe-fnRNA kwigazi le-peripheral kungabi yindinisa kusetyenziswa iindlela eziqhelekileyo zokucoca i-RNA.Iindlela ezisetyenziswa ngokuqhelekileyo ziquka i-NGS, i-microarray kunye ne-RT-qPCR.I-NGS ivumela ii-microRNAs ukuba zilinganiswe kwi-genome yonke.Nangona kunjalo, le ndlela iyabiza kwaye uhlalutyo alufani.Ngokwahlukileyo, i-RT-qPCR ayibizi, ikhulisa ngokukhawuleza i-nucleic acids, kwaye ibonelela ngeenzuzo ezininzi ezinjengobuntununtunu obuphezulu, ukuchaneka okuphezulu, uluhlu olubanzi oluguquguqukayo, kwaye ifuna iisampulu ezimbalwa.IiMicroarrays yenye indlela esetyenziswayo ekubhaqweni kwe-miRNA esekwe kubuntununtunu kunye nokuxutywa okuthe ngqo kwe-miRNA ekujoliswe kuyo kunye ne-probes ye-DNA ehambelanayo, i-75 kodwa uhlalutyo lwedatha ye-microarray idla ixesha.
Ukujikeleza i-miR-122 kunye ne-Let-7 kuye kwaxelwa njengento enokuba luncedo ekuxilongeni i-HCC yangethuba kumaqela asemngciphekweni omkhulu, abamakishi kwizigulane ezine-HBV ezihambelana ne-premalignant nodules kunye ne-HCC yasekuqaleni.76 UCai et al.bafumanise ukuba amalungu osapho lwe-Let-7 (miR-92, miR-122, miR-125b, miR-143, miR-192, miR-16, miR-126, kunye ne-miR-199a/b) basemngciphekweni wokugula okungapheliyo. HCC kwizigulane ezine-hepatitis.Usapho lwe-Let-7 lunokusebenza njenge-biomarker ye-surrogate esebenzayo yokuqikelela ukuphuhliswa kwe-HCC kumaqela asemngciphekweni omkhulu onxulumene ne-hepatitis C engapheliyo. I-77 miR-122 inokuchaneka okuphezulu kokuxilonga ekufumaneni i-HCC yokuqala kwizigulane ezine-cirrhosis yesibindi.I-78 I-Serum ejikeleza i-MiR-107 iye yavavanywa kwakhona kwizigaba zokuqala ze-HCC, i-79 kwaye ibonise amandla amahle kubantu abasengozini enkulu.UZhou et al wabika ukuba iphaneli ye-miRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a kunye ne-miR-801) inokwahlula i-HCC kwi-hepatitis B engapheliyo (CHB) kunye ne-cirrhosis. uvakalelo lwaluyi-79.1% kunye ne-75%, kunye ne-specific 76.4% kunye ne-91.1%, ngokulandelanayo.80 Kwi-HCC enxulumene ne-HBV, sifumene ukuba amanqanaba e-miR150 ancitshiswe kakhulu xa kuthelekiswa nalawo akwizigulane ze-HBV ezingapheliyo ngaphandle kwe-HCC (ubuntununtunu 79.1%, i-76.5%).-224 iphakanyiswe kwi-HCC xa kuthelekiswa nolawulo olunempilo, kwaye uhlalutyo lwe-subgroup lubonise amanqanaba aphezulu kwizigulane ezine-HCC ezinxulumene ne-HBV.I-hepatitis B enxulumene ne-cirrhosis kunye nezigulane ze-HCC zichonge udidi lwe-siRNA oluqulethe ii-siRNA ezisixhenxe ezichazwe ngokwahlukileyo ezinokubona i-HCC kulawulo olwahlukileyo;Uluhlu lwe-AUC ekuhlolweni kwangoko lungcono kunamavolontiya e-AFP.Baye bafumanisa ukuba i-miRNAs ezine (miR-1972, miR-193a-5p, miR-214-3p, kunye ne-miR-365a-3p) inokwahlula izigulane ezine-HCC kwizigulane ezingenayo i-HCC.Ii-miRNA ezinhlanu ezibonisa ngokugqithisileyo (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p, kunye ne-miR-148a-3p) zibhekwa njengezifo ezinokuthi zenzeke kwi-HBV kwi-HCC, i-cirrhosis, kunye ne-CHB biomarkers, ngakumbi i-miR-34a-5p inokuba zii-biomarkers ze-cirrhosis yesibindi, i-85 kwaye inokuba ngamanqaku e-biomarker ekuhlolweni kwangaphambili kwe-HCC kubantu abasengozini enkulu.Eyona lncRNA ifundwe kakhulu kwi-HCC isebenze kakhulu kumhlaza wesibindi (HULC).Olunye uphando lubonise ukuba i-HULC ejikelezayo kwizigulane ze-HCC ingasetyenziswa njengophawu lokuxilonga kuba le lncRNA ilawulwa kakhulu kwizigulane ze-HCC xa kuthelekiswa nabantu abaphilileyo.I-71,86 Phakathi kwezinye ii-lnRNA, i-LINC00152 ithathwa njengeyona nto ingcono yokuxilonga i-lncRNA ngenxa ye-AUC ephezulu, uvakalelo kunye neenkcukacha.86 Kolunye uphononongo, ukubonakaliswa kwegazi kwe-peripheral ye-LINC00152 ngokuthe ngcembe kwanda ukusuka kulawulo oluqhelekileyo olusempilweni ukuya kwizigulane ezine-CHB kunye ne-cirrhosis, kwaye ekugqibeleni yayiphezulu kwi-HCC.Uphononongo lokubonakaliswa kwe-circSMARCA5 kwi-plasma yezigulane ezine-HCC zibonise ukwehla okuqhubekayo kwintetho ye-HCC ukusuka kwi-hepatitis ukuya kwi-cirrhosis kunye nezilonda ze-precancerous.I-87 Uhlalutyo lwe-ROC curves luqinisekisile amandla ala ma-circRNAs ekuhlukaniseni izigulane ezine-hepatitis okanye i-cirrhosis yesibindi kulabo abane-HCC, ngakumbi abo banamanqanaba e-AFP angaphantsi kwe-200 ng / mL.Ukongezelela, u-Zhu uhlalutye i-13,617 ye-cyclic RNAs kwiisampuli ze-plasma ezivela kwizigulane ze-HBV ezinxulumene ne-HCC kwaye yaqinisekisa ukuba i-6 ye-cyclic RNAs ibonakaliswe ngokwahlukileyo kwi-HCC kunye ne-HBV ehambelana ne-cirrhosis, ebonisa ukuba i-cRNA inokuba luncedo.abamakishi bokuhlolwa kwangoko kwamaqela asemngciphekweni omkhulu njengalawo anxulumene nesifo sesibindi, izigulane ze-sclerosis.88
I-Exosomes yi-membrane vesicles 40-160 nm ububanzi;ii-intracellular vesicles ezininzi zixubana ne-membrane yeseli kwaye zikhutshwe kwi-matrix engaphandle.Ziqulethe izinto ezininzi ezisebenzayo, ezibandakanya i-lipids, iiprotheni, i-RNA kunye ne-DNA, kwaye zidlala indima ebalulekileyo ekunxibelelaneni phakathi kweeseli, zombini iiseli ze-HCC kunye ne-non-HCC.I-89,90 Exosomes ilawula ukuqhubela phambili kwe-HCC ngokuvula i-hepatocyte fibroblasts kunye neeseli ze-stellate, iiseli ze-immune, i-hepatocytes eziqhelekileyo, kunye neeseli ze-HCC.91 Kwi-tumor microenvironment, iiseli zethumba zivelisa inani elikhulu leexosomes ezithwalwa ukusuka kwiiseli zomhlaza ukuya kwiiseli ezingekafiki, ezithi nazo zibandakanyeke kwi-oncogenesis, ukuwohloka, kunye nokubonakaliswa kweselula.Izifundo ze-92 zibonise ukuba i-exosomes inokudlulisa i-oncogenes kwiiseli eziqhelekileyo ngexesha leenkqubo ze-pathological, ezinokuthi zibe enye yeendlela zokuhlasela kwe-tumor kunye ne-metastasis.I-93 Indima ye-exosomes ekuqhubekeleni phambili komhlaza inokuba namandla kwaye ikhethekileyo kuhlobo lomhlaza, i-89 Exosomes inokuthi ifakwe ngaphakathi ngamaseli akufutshane okanye akude ukulawula izakhi zofuzo ezininzi ezijoliswe kuzo kwiiseli ezifumanayo ezinokubandakanyeka kwii-ion zonxibelelwano ze-intercellular kunye ne-cellular microenvironment interactions. I-Metabolism kunye ne-Metabolism ye-Metabolism.Iimpawu ze-94 kunye notshintsho oluguquguqukayo lwe-exosome cargo molekyuli zibonakalisa ngokuthe ngqo iimpawu kunye notshintsho oluguquguqukayo lweeseli zethumba labazali, i-95 ekwasisiseko sokusetyenziswa kwe-exosomes ekuxilongweni kunye nokuxilongwa komhlaza, kunye nokuxela kwangaphambili impendulo yomntu kunyango lwe-anticancer. ..96
Iindlela zebhubhoratri eziqhelekileyo zokuzihlukanisa kunye nokuhlalutya i-exosomes ziyinkimbinkimbi, i-multi-step, kunye nexesha elide, kubandakanywa i-ultracentrifugation, i-filtration, i-chromatography yokukhutshwa kobungakanani, ukuhlanjululwa kwe-immunoaffinity, ukuchithwa kwe-Western, i-enzyme-linked immunosorbent assay (ELISA), i-PCR, kunye nohlalutyo lokuhamba.iinkqubo ezincinci kunye namaqonga e-lab-on-a-chip asebenzisa i-micro/nanotechnology ziphuhliswa ngokubanzi ukuze zikhawuleze, zilungele ukubekelwa bucala kwee-exosomes kwindawo.Uhlalutyo lokulandela umkhondo we-Nanoparticle (NTA) yindlela esetyenziswa ngokubanzi yokubonakalisa ubungakanani kunye nokuxinana kwee-exosomes, kubandakanywa neendlela ezifana ne-magnetic nanoparticles kunye ne-polyhydroxyalkanoates.Iindlela zeMicrofluidic kunye ne-electrochemical nazo ziyakwazi ukubona ngokukhawuleza i-exosomes kwizivuno eziphezulu.
Iiprotheyini ze-Exosomal ziziphawuli ezibalulekileyo zokuxilongwa kwe-HCC.Kwisifundo se-Arbelaiz, inqanaba le-98 RasGAP SH3 yokubopha iprotheni (G3BP) kunye ne-polymeric immunoglobulin receptor (PIGR) yayiphakanyiswe kakhulu kwi-HCC-derived exosomes, kwaye i-puative edibeneyo edibeneyo yeeprotheni ezimbini yayiphezulu kune-AFP.Ukugcwala kwentsimbi ngumba obalulekileyo onegalelo kuphuhliso lwe-HCC.UTseng uxele ukuba i-hepcidin inokudlala indima ephambili ekuchaseni i-HCC.Ii-Exosomes ezingama-99 ezithathwe kwi-sera yezigulane ze-HCC zinenani eliphezulu kakhulu lekopi yee-hepcidin mRNA ezahlukeneyo kunezabo ezisempilweni, ecebisa ukuba i-hepcidin inokuba yinoveli yoxilongo lwe-biomarker ye-HCC.Iprotheni ye-14-3-3ζ kwii-exosomes eziveliswa yi-100 HCC inokunciphisa ukusebenza kwe-T cell, ukwanda, kunye nokwahlula kwaye inokubangela ukuguqulwa kweeseli ze-T kwiiseli ze-T ezilawulayo, okubangelwa ukuchithwa kweeseli ze-T.101 Oku kuxhaswa luphononongo oluninzi oluphanda ukubaleka kwethumba kuphononongo lwamajoni omzimba, i-102 enokuthi ibe negalelo kwi-HCC tumorigenesis.
Ukongeza kubukho be-ecRNA kwiplasma okanye kwiserum, ii-exosomes ezityetyisiweyo ze-RNA zinokusetyenziselwa ukungahlaseli okwexesha lokwenyani ekuhlolweni kwangaphambili kwethumba kunye nokumisela ukuvela kwethumba kunye nokuphendula kunyango.Inqanaba le-exosomal miRNA-21 kwi-serum yegazi kwiqela le-HCC laliphezulu ngamaxesha angama-2.21 ngaphezu kweqela le-CHB, kwaye kwiqela le-HCC laliyi-5.57 ngamaxesha aphezulu kunabantu abanempilo.Kuphononongo lweWang, i-exosomes yonyusa kakhulu i-HCC xa kuthelekiswa nezigulana ze-cirrhotic ezinexabiso le-AUC le-0.83 (95% CI 0.74-0.93) kunye ne-0.94 (95% CI 0.88-1.00).I-104 Idatha efunyenweyo icacise ukubandakanyeka kwee-athomu ezithile ze-exosomal cargo kulawulo lwe-oncogenesis kunye nokuqhubekela phambili kwe-HCC.105 Ukubonakaliswa kweSerum ye-miR-221, miR-103, miR-181c, miR-181a, miR-93 kunye ne-miR-26a iyahambelana.kunye ne-metastasis, kunye namanqanaba e-miR21 ayephezulu kakhulu kwizigulane ze-HCC kunezolawulo olunempilo kunye nakwizigulane ze-CHB.Uphononongo lubonise ukuba i-exosomes evela kwi-sera yezigulane ze-HCC zinamanqanaba aphezulu kakhulu e-LINC00161, i-LINC000635, kunye ne-lncRNA esebenzayo ngokuguqula ukukhula kwe-β kunezigulane ezingenayo i-HCC, kwaye ezi lncRNAs zihambelana kakhulu nesigaba se-TNM kunye nomthamo we-tumor.110 Conigliaro et al.I-CD90 + exosomes ifunyenwe ukubonisa amanqanaba aphezulu e-lncRNAH19, eyandisa kakhulu ukukhutshwa kwe-vascular endothelial growth factor (VEGF) kunye neVEGF-R1 imveliso ye-receptor, ngaloo ndlela ivuselela i-angiogenesis.I-93 CircRNAs yolunye uhlobo lwe-ncRNAs ye-exosomal - echazwe kumanqanaba aphantsi kodwa azinzileyo kuzo zonke iintlobo zeentlobo, ii-circRNAs nazo zibonisa uhlobo oluthile lweseli, uhlobo lwezicubu, isigaba sophuhliso, kunye nomsebenzi wokulawula.Ii-circRNA eziyi-111 ziziphawulo zebhayoloji zokuxilongwa kwangoko kunye nomhlaza ohlaselayo omncinci.I-112 yolingo lwakutsha nje lwezonyango lubonise ukuba ukuchaneka kwe-miRNAs nganye ekucingeleni i-HCC ayilunganga.Ngoko ke, ukufumanisa okuyinkimbinkimbi kusetyenziswa ii-assays ezininzi (umzekelo, i-miR-122 kunye ne-miR-48a ngokudibanisa ne-AFP) kunokuphucula ukuchongwa kwe-HCC yokuqala kunye nokwahlula kwe-HCC kwi-cirrhosis.100
Izigulane ezine-CHB kunye ne-cirrhosis yesibindi liqela eliqhelekileyo elinomngcipheko ophezulu wokuphuhlisa i-HCC.Kumaqela asemngciphekweni omkhulu, emva kokuba impendulo eqhubekayo ye-virological ifezekisiwe, isicwangciso sokuhlola indleko esekelwe kwingozi ye-HCC kufuneka siphuhliswe, kwaye ukuhlolwa kwangaphambili kungundoqo ekuphuculeni ukuxilongwa kunye nokunyangwa kwe-HCC kunye nexabiso eliphezulu le-2. ..Iindlela zokuhlola kwangethuba umhlaza zinemida emininzi: iindlela ezisebenzayo zokuhlola kwangethuba azikaphuhliswa kuninzi lweentlobo zomhlaza, kwaye ubambelelo ludla ngokuba phantsi.Xa kuthelekiswa neendlela zovavanyo lwakwangoko, itekhnoloji ye-biopsy yolwelo ineengenelo ezicacileyo: ukulula kwesampulu, ukuchongwa kwe-panrac, ukuveliswa kwakhona kwesampulu elungileyo, kunye nempendulo esebenzayo kwi-tumor heterogeneity.Ukunikezelwa kweendleko-zokusebenza kweendlela ezinxulumene ne-liquid biopsy, ukusetyenziswa kwazo ekuhlolweni kwe-HCC akuzange kuhlolwe rhoqo.Ngaphandle kwenkqubela phambili ekubhaqweni ngokuchanekileyo kwinqanaba le-molecular, i-biopsy ye-fluid iyabiza ukufumanisa i-HCC kwizigulana ezijoliswe kuyo, ukunciphisa ukusetyenziswa kwayo ngokubanzi xa kuthelekiswa neenkqubo zokucinga ezithile ezifana ne-ultrasound kunye ne-imaging resonance magnetic.I-113,114 Nangona kunjalo, uphando lwangaphambili lubonise ukuba i-biopsy ye-liquid ibonise inzuzo ebalulekileyo ngokweminyaka yobomi obulungelelanisiweyo (QALYs).115 Iinzuzo ze-biopsy yolwelo kwi-carcinoma yokuqala yesisu kunye ne-nasopharynx nazo zibonisiwe.I-116,117 Imbono yangoku kukuba i-biopsy yolwelo ingancedisana ne-serum biomarkers kunye nokuhlolwa kwe-radiological ekubhaqweni kunye nokuxilongwa kwamathumba.117 118
Ngokoncwadi lwangoku, itekhnoloji ye-biopsy ye-fluid ibonise ubuntununtunu obuphezulu kunye nokukodwa ekuhlolweni kwangoko kwamaqela asemngciphekweni omkhulu womhlaza wesibindi.Nokuba luhlobo luni na lwe-biopsy yolwelo, inokwahlula i-HCC kubantu abasengozini enkulu ngaphandle kwe-HCC, icebisa ukubaluleka kovavanyo kwangoko njengoko umahluko phakathi kwabantu abasengozini enkulu kunye nabasempilweni uyabonakala.I-ctDNA inobomi obufutshane obufutshane kwaye ingasetyenziselwa ukubona i-HCC, ngoko ke naluphi na utshintsho kwi-cDNA ephuma kwithumba inokubonelela ngobungqina bexesha lokwenyani lokuqhubela phambili kwethumba, ngakumbi kumathumba amancinci.Inqanaba eliphezulu le-ctDNA libonisa ukukhula kunye nokusasazeka komhlaza kwaye sisalathiso sakwangoko sokuqhubela phambili kunye nokuphindaphinda.Ukongeza, ngokusekelwe kwiziphumo ze-ctDNA, izigulane zinokufumana unyango lomntu ngamnye kunye nokulandelwa.Iisayithi ze-119 ezikhethekileyo ze-methylation zinokuba ngumqondiso ongcono kune-AFP yokuchongwa kwangaphambili kwe-HCC kunye ne-cirrhotic nodules.Kwiimeko ezihlaziyiweyo ze-HCC, amanqanaba aphezulu e-cDNA abonisa ukuhlaselwa kwe-microvascular kunye nokuphindaphinda emva kokusebenza kunye ne-metastasis.Utshintsho kwinombolo yekopi lunxulunyaniswa nokusinda kwezigulane ezine-HCC.Kungacingelwa ukuba uvavanyo lwe-cDNA lunokubandakanyeka kunyango olupheleleyo lwe-HCC, kwaye i-cDNA inokusebenza njengesalathisi esisebenzayo sokumodareyitha kwezonyango.Amanqaku asekelwe kwiinguqu ezithile zemfuza kwi-ctDNA zamkelwe zizikhokelo zeklinikhi ukuqikelela ukusebenza kunye nokubeka iliso kuxhathiso lwamachiza.Uvavanyo lwe-ctDNA inokuba sesona sixhobo siluncedo se-biopsy yolwelo ekuhlolweni kwangoko.Ii-CTC nazo zidlala indima ephambili ekuhlolweni kwangaphambili kwamaqela e-HCC asemngciphekweni omkhulu.Iimpawu ezahlukeneyo zee-CTC ezinxulumene ne-HCC zibaluleke kakhulu ekuqaleni, uphuhliso, kunye nokuphindaphinda kwe-HCC.Njengee-membrane vesicles, i-exosomes ibandakanyeka kunxibelelwano lwe-intercellular, ngakumbi kwiiseli ze-HCC.Ii-microRNAs ezijikelezayo zizinzile egazini kwaye ke zinokuba luncedo ngakumbi ekuhlolweni kwangoko kwe-HCC.Kancinci, iiprotheyini ze-exosomal kunye ne-RNA-rich exosomes zafunyanwa, kunye nokusebenza kwazo kwangaphambili kwe-HCC kwaqinisekiswa.Okubangela umdla kukuba, ii-etiologies ezahlukeneyo ze-HCC zinokunxulunyaniswa notshintsho olwahlukileyo, ngoko ke sinokukhetha ii-biomarkers ezahlukeneyo zovavanyo lwakwangoko olusekwe kwii-etiologies ezahlukeneyo ze-HCC.120
Nangona kunjalo, iindlela zangoku ze-biopsy zolwelo ziyathandabuzeka ngokozinzo kwaye azikwazi ngokuzimeleyo ukwenza uvavanyo kwangethuba okanye ukubeka iliso kwi-HCC, kodwa zisenokuncedisana novavanyo lomntu ngamnye kunye noxilongo.121 Njengohlobo lwe-biopsy yolwelo, ukufunyaniswa kunye nokwenziwa kwe-ctDNA, i-CTC, i-cfRNA kunye ne-exosome ehambelana ne-AFP okanye i-PIVKA-II inezicelo ezithembisayo ekuxilongeni kwangaphambili kunye noxilongo lwe-HCC.Nangona kunjalo, indlela echanekileyo yokukhutshwa kwe-ctDNA egazini kusafuneka icaciswe.Ukutyhila iimpawu zebhayoloji ezisisiseko ze-ctDNA kunokuququzelela ukusetyenziswa kwayo njengesiphawuli.Isixa esincinci se-ctDNA ekujikelezeni kunye neemfuno ezingqongqo zokuphatha isampula yimingeni yokuphunyezwa kweklinikhi yokufunyanwa kwe-cDNA kwi-HCC.Ukongezelela, ukuguqulwa kofuzo alunazo iimpawu ezithile ezivumela ukuchongwa ngokuchanekileyo kwe-carcinogens.Kuba iinguqu ezininzi zemfuza kunye ne-somatic zikhona kwizicubu eziqhelekileyo, utshintsho lwemfuza oluchongwe yi-fluid biopsy lunokuba luncedo olulinganiselweyo ekuhlolweni kwangaphambili kwe-HCC.I-122 Imida yeethagethi ze-gene eziluncedo ezichazwe kakuhle kunye ne-biomarkers ezinceda ukwahlula i-cDNA kwi-DNA engeyiyo i-tumor yeyona miba ibaluleke kakhulu ekusebenziseni i-cDNA.ukunqongophala kokusebenziseka kwezinto ezinovakalelo kunye neziphawuli ezithile zokuchongwa kwee-CTCs.Kuphela ziiseli ezisebenzayo ezinesakhono semetastatic ezifunyenweyo, kwaye indibaniselwano ilungileyo yeCSC etyetyisiweyo yamanqaku ibingacacanga.Ukwahlulwa kwee-CTC zenkcubeko kunye novavanyo lweeprofayili zazo eziguqukayo nako kungumsebenzi ocela umngeni.Ngenxa yeengxaki zokuchongwa, ukuhlukaniswa kunye nokucocwa kwee-exosomes, indlela ethile ye-molecular ayikacaci, kwaye izifundo zangaphambili malunga nendlela ye-exosomes kunye ne-HCC azizange zibe nzulu, kunye nendlela i-miRNAs, i-lncRNAs, kunye neeprotheni ezihlelwe zibe yi-exosomes. , kwaye akucaci ukuba i-exosome uptake yinkqubo yohlobo oluthile.Ukusetyenziswa kwe-exosomes yokuxilongwa kunye nonyango lwe-HCC kusekho kwinqanaba lokuqala.Ukungabikho komgangatho weenkqubo ze-biopsy zamanzi, ezifana nohlobo lweetyhubhu ezisetyenziselwa ukuqokelela igazi, umthamo wegazi, ukugcinwa kwesampulu kunye nokufumanisa, ukuhlukaniswa kunye nokutyebisa, kunokuthintela ukusetyenziswa kwabo kwisiqhelo seklinikhi ngenxa yokungafani kweendlela zokusebenza kumaziko onyango.Ukusebenza kwe-biopsy yolwelo ekuhlolweni kwangaphambili, ukuxilongwa, ukuvavanya ukusebenza kakuhle, kunye nokuqikelelwa kwangaphambili kwe-HCC kusaza kuphononongwa, ngakumbi kumaqela asemngciphekweni omkhulu.Itekhnoloji ye-biopsy yolwelo inamandla amakhulu kwaye kulindeleke ukuba isetyenziswe ngokubanzi kunyango lomhlaza wesibindi kungekudala.
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