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UDing Jingnuo, u-Zhao Weifeng, uMnyango Wezifo Ezithathelwanayo, Isibhedlela Esihlanganisiwe SeYunivesithi YaseSuzhou, Idolobha LaseSuzhou, Isifundazwe saseJiangsu, 215000 Ucingo.Izimila zesistimu yokugaya ukudla okuneminyaka engu-5 yokuphila okuphelele kwe-14.1%.Iziguli eziningi ezine-HCC zitholwa zisezingeni eliphezulu, ngakho ukuhlolwa kusenesikhathi kubalulekile ukuze kwehliswe ukufa kwabantu ngenxa ye-HCC.Ngaphezu kwezinkomba ezijwayelekile ezisetshenziswayo ezifana ne-serum alpha-fetoprotein (AFP), i-lens lectin-reactive alpha-fetoprotein (AFP-L3), kanye ne-prothrombin engavamile (i-vitamin K ebangelwa ukuntuleka kwe-protein II, i-PIVKA-II), amasu e-fluid biopsy. Kuboniswe ukuthi inenani lokuxilonga ekutholweni kwe-HCC.Uma kuqhathaniswa nezinqubo ezihlaselayo, i-fluid biopsy ingathola ama-metabolites amabi ajikelezayo.Amasu e-Fluid biopsy athola amaseli wesimila ajikelezayo, i-DNA yesimila esijikelezayo, i-RNA ejikelezayo, nama-exosomes futhi asetshenziselwa ukuhlolwa kusenesikhathi, ukuxilongwa, nokuhlola okubikezelwe kwe-HCC.Lesi sihloko sibuyekeza i-molecular biology kanye nokusetshenziswa kwamasu ahlukahlukene e-fluid biopsy ukuze ahlukanise ama-biomarker athembisayo angaba izinketho ezisebenzayo zokuhlolwa kwangaphambi kwesikhathi kwe-HCC ukuze kuthuthukiswe ukuhlolwa kwangaphambi kwesikhathi kwamaqembu e-HCC asengozini enkulu.Amagama angukhiye: inqubo ye-fluid biopsy, i-hepatocellular carcinoma, iqembu eliyingozi kakhulu.
I-Hepatocellular carcinoma (HCC) yisimila esiyingozi esivamile somgudu wokugaya ukudla, sikleliswe endaweni yesithupha phakathi kwezigameko ezintsha zezimila eziyingozi kubo bobabili abesilisa nabesifazane.1 Emhlabeni wonke, umdlavuza wesibindi uyimbangela yesithathu ehamba phambili yokufa komdlavuza ngemva komdlavuza wamaphaphu nowomdlavuza wekoloni, ubala u-8.3% wokufa okuhlobene nomdlavuza kuwo wonke ama-neoplasms ayingozi.1 Ukubikezelwa kwe-HCC kuhlobene eduze nesigaba sokuxilongwa.Izizathu eziyinhloko zokusinda kabi ku-HCC ama-metastase e-intrahepatic, i-portal venous tumor thrombi, nama-metastases akude avimbela ukukhishwa kabusha, futhi eziningi zalezi zici sezivele zikhona ezigulini ngesikhathi sokuxilongwa.
Ngokusekelwe eziqondisweni zokuxilonga nokwelashwa, izici eziyinhloko eziyingozi ekuthuthukiseni i-HCC ukuqina kwesibindi, i-Chronic hepatitis B virus (HBV) noma i-hepatitis C virus (HCV), isifo sesibindi esinamafutha e-alcoholic, nesifo sesibindi esinamafutha angenalo utshwala (NAFLD ).2 Ngaphezu kwalokho, izici eziyingozi ze-HCC zihlanganisa ukudla okune-aflatoxin, i-schistosomiasis, ezinye izimbangela ze-cirrhosis, umlando womndeni womdlavuza wesibindi, isifo sikashukela, ukukhuluphala, ukubhema, nokulimala kwesibindi okubangelwa izidakamizwa.Amaqembu asengozini enkulu eneminyaka engama-35 no-45 kufanele ahlolwe njalo udokotela.Ukuhlolwa kusenesikhathi kuyisu elibalulekile lokwelapha kusenesikhathi ukuthuthukisa ukusinda kukonke kweziguli ezine-HCC.
Ama-Biomarker afana ne-AFP, AFP-L3 ne-PIVKA-II ayanconywa ukuze kuhlolwe kusenesikhathi kwe-HCC3,4.Amasu we-Liquid biopsy abonise imiphumela ethembisayo ekuxilongweni kusenesikhathi nokuhlolwa kokwelashwa.5,6 Inqubekelaphambili enkulu yenziwe ku-HCC liquid biopsy, okungenzeka ibe nokuzwela okuphezulu nokucaciswa kunezimpawu zeserum ezivame ukusetshenziswa njenge-AFP (Ithebula 1).
I-AFP iyi-biomarker esetshenziswa kabanzi ku-HCC futhi njengamanje iyi-biomarker enemininingwane eminingi esetshenziswa kabanzi ekuhlolweni kusenesikhathi, ekuxilongeni nasekuhlolweni kwalesi sifo.Izinga le-AFP eliqhubekayo libhekwa njengento eyingozi yokuqhubekela phambili kwe-HCC.I-7,8 Izinga lokutholwa kwe-hepatocellular carcinoma (sHCC) liyanda ngokuthuthukiswa kwe-ultrasound kanye ne-computed tomography, futhi i-AFP itholakale ingenandaba ikakhulukazi ekutholeni i-hHCC emisebenzini yomtholampilo.Ngokocwaningo lwe-retrospective multicentre9, i-AFP positive itholwe ku-46% (616/1338) wamacala e-HCC kanye nama-23.4% (150/641) wamacala e-sHCC.Ngaphezu kwalokho, amazinga e-AFP aphakanyisiwe ezigulini ezinesifo sesibindi esingamahlalakhona kanye ne-cirrhosis.10 Ngakho, i-AFP inomphumela olinganiselwe wokuhlola we-sHCC.11 Ngokusho kwe-Asia-Pacific Clinical Practice Guidelines for Hepatocellular Carcinoma, ukusetshenziswa kwe-AFP akukhuthazwa.12 Ubufakazi bomtholampilo bubonisa ukuthi i-PIVKA-II iphakeme kune-AFP ekwelapheni i-HCC nokuthi inhlanganisela ye-PIVKA-II ne-AFP ine inani eliphakeme lokuxilonga ku-HCC.13 Uma kuqhathaniswa ne-tissue biopsy, i-fluid biopsy ithola ngokuyinhloko ama-metabolite ahlobene nesimila oketshezini lomzimba (igazi, amathe, uketshezi lwe-pleural, uketshezi lwe-cerebrospinal, noma umchamo) futhi ayihlaseleki kancane ezicutshini.14 Ngaphezu kwalokho, ama-biopsy oketshezi angase abonise izici eziyingozi ezingekho esiculweni sokuqala sesimila.15 I-Liquid biopsies ayikahlolisiswa emtholampilo yazo zonke izinhlobo zamathumba, kodwa amandla awo okuxilonga kumdlavuza adonsa ukunaka kodokotela be-oncologist.16 I-Fluid biopsy ingathola amaseli wesimila ajikelezayo (CTCs), i-circulating tumor DNA (cDNA), ezungeza i-RNA yamahhala (ecRNA), nama-exosomes.Kulesi sihloko, sizoxoxa ngezici, indima, kanye nokusetshenziswa kwamasu ahlukahlukene e-biopsy oketshezi ekuhlolweni kwangaphambi kwesikhathi kwamaqembu e-HCC asengozini enkulu.
I-DNA ye-Extracellular (cfDNA) kumasampula egazi avela kubantu abanempilo yachazwa okokuqala ngo-1948 nguMandel et al.I-17 cfDNA iwucezu lwe-DNA engenamaseli cishe ubude obuyi-160–180 bp, olusuka ikakhulukazi kuma-lymphocyte namaseli e-myeloid.I-ctDNA iwucezu oluthile lwe-DNA eguquguqukayo olukhishwe amaseli wesimila egazini le-peripheral, elimele ulwazi lwe-genomic lwamaseli wesimila ngemva kwezinqubo ezithile ze-pathophysiological, okuhlanganisa i-necrosis, i-apoptosis, nokuphuma.Ingxenye ye-ctDNA ku-cfDNA iyonke iyahluka kakhulu ngohlobo lwesimila, futhi izingcezu ze-cDNA kubikwa ukuthi ngokuvamile zingaphansi kuka-167 bp ubude.18 Ucwaningo luka-Underhill lubonise ukuthi izingcezu ze-cfDNA ngokuvamile zimfushane kune-cfDNA evamile.19 Uma kuqhathaniswa nabantu abanempilo, ubude obuphelele bezingcezu ze-cfDNA egazini leziguli ezinomdlavuza bufushane, ngakho i-cfDNA ingasetshenziswa njengenkomba yokuhlolwa kwesimila kwasekuqaleni.Ukunothiswa kwamasethi athile angaphansi wobude besiqephu se-cfDNA kungathuthukisa ukutholwa kwe-cDNA ehambisana nezimila eziqinile ezingezona eze-metastatic.Ucwaningo luye lwabonisa ukuthi i-ctDNA itholakala ngaphezu kwama-75% omdlavuza we-pancreatic, i-colon, esinyeni, i-gastrointestinal, isibindi, i-ovary, ibele, i-melanoma, kanye nomdlavuza wekhanda nentamo.20,21 Nokho, inani le-ctDNA egazini lincike endaweni yesimila.22 Ocwaningweni olwenziwa ngu-Bettegoud, iziguli ezinomdlavuza we-colorectal, webele, wesibindi, wamaphaphu, nowe-prostate zitholakale zinamazinga aphezulu e-cDNA egazini lazo kuneminye imidlavuza.Ngokuphambene, ezigulini ezinomdlavuza womlomo, umdlavuza we-pancreatic, umdlavuza wesisu, ne-glioma, ukuhlushwa kwe-cDNA egazini kwakuphansi.amashumi amabili nanye
Ngenxa yokuthi i-ctDNA iqukethe ukuguqulwa kofuzo okufanayo njengamaseli wesimila ayinhloko, i-cDNA ingasetshenziswa ukuthola ukuguquka okuhlukile kwe-tumor okukhethekile kanye nezinguquko ze-epigenetic, okuhlanganisa i-methylation, i-hydroxymethylation, ukuhluka kwe-nucleotide eyodwa, nokuhluka kwenombolo yokukopisha.amashumi amabili nantathu
I-DNA methylation ingenye yezinguquko ezivame kakhulu ze-epigenetic eziholela ekucindezelweni kofuzo.Uma kuqhathaniswa namangqamuzana avamile, kunomehluko ezingeni eliphelele le-methylation ye-tumor cell genome, ikakhulukazi ku-methylation yezakhi zofuzo ze-tumor suppressor, ezingatholakala kusenesikhathi, okuphakamisa ukuthi izinguquko ku-DNA methylation zingase zibe inkomba yokuqala. ukutholakala kwe-tumorigenesis.Izakhi zofuzo ezicindezela i-tumor ezihambisana ne-HCC zingenziwa zingasebenzi ngomgqugquzeli we-methylation, ngaleyo ndlela kukhuthaze i-tumorigenesis.24 I-DNA methylation iwumaka ofanelekile wokuhlonza amathumba ngaphambi kwesikhathi ngenxa yokucaciswa kwawo kwezicubu, ukubonwa, nokuzimela kweminyaka.Ukwengeza, i-DNA methylation ivame kakhulu uma iqhathaniswa nokuguqulwa kwe-somatic ngoba kunezifunda eziningi ezihlosiwe kanye nezindawo ezimbalwa ze-CpG eziguquliwe esifundeni ngasinye segenome eqondiwe.25 Ngokungeziwe kumasayithi amaningi e-CpG, inani elikhulu le-hypermethylated loci ezimele ku-ctDNA likhonjwe ku-DBX2, THY1, MT1M, INK4A, VIM, FBLN1, kanye ne-RGS10.26 Xu et al.Ukuqhathaniswa kwamasampula e-cfDNA avela ezigulini eziyi-1098 HCC kanye nezilawuli ezinempilo ezingama-835 kwakuyizakhi zofuzo ezihlotshaniswa ne-HCC kutholwe kuhlobana kakhulu namasignesha ahambisanayo e-plasma cDNA methylation.25 Ngokusekelwe ekuhlaziyweni kwaselabhorethri, imodeli yokubikezela yathuthukiswa equkethe izimpawu ze-methylation eziyi-10 ezinokuzwela kanye nokucaciswa kwe-85.7% kanye ne-94.3%, ngokulandelana, futhi lezi zomaka zazihlotshaniswa kakhulu ne-tumor mass, isigaba sesimila, kanye nokuphendula ekwelashweni.Le miphumela ikhombisa ukuthi ukusetshenziswa kwezimpawu ze-cDNA methylation kunesithembiso esikhulu ekuxilongweni, ekuqapheni, nasekuqaguleni kwe-HCC.Kumodeli ye-methylation ehlanganisa izakhi zofuzo ezintathu ze-aberrantly methylated (APC, COX2, RASSF1A) kanye ne-miRNA eyodwa (miR203) eyethulwe ngu-Lu et al27, ukuzwela nokucaciswa kwemodeli 27 yokuhlonza i-HBV ehlobene ne-HBV kwakuqhathaniswa.80%.Ngaphezu kwalokho, imodeli ingathola u-75% weziguli ze-HCC ezingakahlonzwa ezinezinga le-AFP lika-20 ng/mL.Isakhi sofuzo somndeni wesizinda esihlotshaniswa ne-Ras i-1A protein (RASSF1A) iwukulandelana okuyinhloko kwe-DNA ephindaphindayo ku-genome yomuntu.U-Araujo et al.waphetha ngokuthi i-hypermethylation yomgqugquzeli we-RASSF1A ingaba i-biomarker ebalulekile yokuhlolwa kusenesikhathi kwe-HCC kanye nethagethi ye-molecular engaba khona yokwelashwa kwe-epigenetic.28 Ocwaningweni olulodwa, i-serum RASSF1A umgqugquzeli we-hypermethylation yatholakala ku-73.3% weziguli ezine-HCC.29 Ingxenye 1 ye-nucleotide ene-interspersed ende (LINE-1) ingenye i-retrotransposition mediator esebenza kakhulu.I-Hypomethylation ye-LINE-1 itholwe ku-DNA ye-66.7% yamasampuli e-HCC serum futhi yayihlotshaniswa nokuphindaphinda kwangaphambi kwesikhathi kanye nokusinda okungekuhle ngemva kokukhishwa kabusha okukhulu.29 I-Hypermethylation iyinqubo evamile yofuzo edlala indima eyingqayizivele ekuthuthukiseni i-cirrhosis yesibindi ne-HCC.30 Ngokuphambene, i-hydroxymethylation iyinqubo ye-demethylation eyenza ukuvuselelwa kofuzo nokuvezwa, futhi ukutholwa komkhiqizo we-5-hydroxymethylcytosine (5-hmC) kule nqubo kungasetshenziswa ukukhomba isimila.I-Methylation ne-hydroxymethylation ye-cDNA ihlotshaniswa ne-tumorigenesis futhi ingaba nomthelela ekuhlolweni kokuqala kwe-HCC.Ocwaningweni lwezifundo ezingama-2554, ama-31 genome-wide 5-hmCs atholakala kumasampula e-cfDNA, futhi izakhi zofuzo ze-32 zikhonjwe ngokuqhathanisa ukulandelana kwe-5-hmC ezigulini ze-HCC kanye namaqembu asengozini enkulu njengalawo anezifo ezingapheli.Izindlela zokuxilonga zezifo zesibindi.kanye ne-cirrhosis.Le modeli yayingcono kune-AFP ekuhlukaniseni i-HCC nezicubu ezingezona izimila.
Ukuguqulwa kwezakhi ezifundeni zokufaka amakhodi kungaholela ekubhaleni okungajwayelekile, okungaholela ezinguqukweni zokulandelana kwamaprotheni futhi ekugcineni kube nomdlavuza.Izinhlobonhlobo ze-nucleotide eyodwa ziyizimpawu ezibalulekile ze-genomic zokuhlolwa kwangaphambi kwesikhathi kwesimila ngenxa yokuthembeka kwazo okuphezulu kwezicubu kanye nokucaciswa kwesimila okuphezulu kanye nezicubu.Ucwaningo oluningi oluhlobene ne-HCC kusetshenziswa ukulandelana kwesizukulwane esilandelayo (NGS) kwe-exome kanye nokulandelana kwe-genome okuphelele komdlavuza kukhombe izakhi zofuzo ezivamile zamaselula eziguquliwe njenge-TP53 ne-CTNNB1, kanye nezimbalwa ezihlanganisa i-ARID1A, MLL, IRF2.Izakhi zofuzo ezintsha, i-ATM, i-CDKN2A, i-FGF19, i-PIK3CA, i-RPS6KA3 ne-JAK1 ibonisa amazinga okushintsha amaphakathi. Ukuhlaziywa kokusebenza kwezakhi zofuzo eziguquguqukayo kuphakamisa ukuthi izinguquko ekulungisweni kabusha kwe-chromatin, i-Wnt/β-catenin kanye ne-JAK/STAT yesignali, indlela yomjikelezo we-P53-cell, ama-epigenetic modifiers, izindlela ze-oxidative stress, indlela ye-PI3K/AKT/MTOR kanye ne-RAS/RAF/ I-MAPK kinase pathway idlala indima ebalulekile ku-HCC oncogenesis.32,33 Ocwaningweni lapho ukuguqulwa okuhlobene ne-tumor kutholwe khona, u-Huang et al wathola ukuthi imvamisa yokuguqulwa kwe-tumor okuhlobene ne-ctDNA yayingu-19.5%, futhi okucacile kwakuyi-90% .34 Ngaphezu kwalokho, iziguli eziye zahlaselwa yimithambo zazingase zibe nokuguqulwa kwe-ctDNA (P=0.041) kanye nokusinda okufushane okungaphindeki (P<0.001). Ukuhlaziywa kokusebenza kwezakhi zofuzo eziguquguqukayo kuphakamisa ukuthi izinguquko ekulungisweni kabusha kwe-chromatin, i-Wnt/β-catenin kanye ne-JAK/STAT yesignali, indlela yomjikelezo we-P53-cell, ama-epigenetic modifiers, izindlela ze-oxidative stress, indlela ye-PI3K/AKT/MTOR kanye ne-RAS/RAF/ I-MAPK kinase pathway idlala indima ebalulekile ku-HCC oncogenesis.32,33 Ocwaningweni lapho ukuguqulwa okuhlobene ne-tumor kutholwe khona, u-Huang et al wathola ukuthi imvamisa yokuguqulwa kwe-tumor okuhlobene ne-ctDNA yayingu-19.5%, futhi okucacile kwakuyi-90% .34 Ngaphezu kwalokho, iziguli eziye zahlaselwa yimithambo zazingase zibe nokuguqulwa kwe-ctDNA (P=0.041) kanye nokusinda okufushane okungaphindeki (P<0.001).Ukuhlaziywa kokusebenza kofuzo oluguquguqukayo kuphakamisa ukuthi izinguquko ekulungisweni kabusha kwe-chromatin, ukusayinda kwe-Wnt/β-catenin kanye ne-JAK/STAT, indlela yomjikelezo wamaseli e-P53, ama-epigenetic modifiers, izindlela ze-oxidative stress, indlela ye-PI3K/AKT/MTOR, kanye ne-RAS/RAF/MAPK/MAPK indlela yokudlala. indima ebalulekile ku-HCC tumorigenesis.32,33 Ocwaningweni oluthola ukuguqulwa kwe-tumor-associated, u-Huang et al.ithole ukuthi imvamisa yokuguqulwa kwesimila esincike ku-ctDNA yayingu-19.5% futhi ukucaciswa kwakungama-90%..34 I-Кроме того, у пациентов сосудистой инвазией чаще встречались мутации цДНК (P=0,041) futhi более короткая безрецивыдиживя , 0,041 (1). .34 Ngaphezu kwalokho, iziguli ezine-vascular invasion zazinezinguquko eziningi ze-cDNA (P=0.041) kanye nokuphila okufushane okungenasifo (P<0.001).Ukuhlaziywa okusebenzayo kwezakhi zofuzo eziguquguqukayo kwembule ukulungiswa kabusha kwe-chromatin, ukusayinda kwe-Wnt/β-catenin kanye ne-JAK/STAT, indlela yomjikelezo wamaseli e-P53, ama-epigenetic modifiers, indlela ye-oxidative stress, indlela ye-PI3K/AKT/MTOR, kanye ne-RAS/RAF/MAPK i-kinase pathway idlala indima ebalulekile ku-oncogenesis ye-HCC. 32,33 在在 项项 肿瘤 肿瘤 肿瘤肿瘤 的 的 的 的 研究 中 研究中,突变（P=0.041）和更短的无复发生存期（P<0.001) 32.33 在在 项项 到 到检测 突变突变 研究 的 的研究, Huang 等 发现 肿瘤肿瘤短的无复发生存期（P<0.001)32,33 Ocwaningweni oluthole ukuguqulwa okuhlobene nesimila, u-Huang et al.ithole ukuthi ukuguqulwa kwe-tumor-associated kwakungu-19.5% kuncike ku-cDNA enemininingwane ye-90% 34. Ngaphezu kwalokho, iziguli eziye zahlaselwa yi-vascular zazivame ukuthuthukisa i-cDNA.мутация (P = 0,041) kanye ne-более короткая безрецидивная выживаемость (P <0,001). ukuguqulwa (P=0.041) nokuphila okufushane okungenazifo (P<0.001).Olunye uhlobo lomshayeli oluvamile lwe-HCC yi-TP53, enezinga lokuguqulwa elingaphezu kuka-30%.Ucwaningo lubonise ukuthi imvamisa yokuguqulwa kwe-TP53 ku-ctDNA egazini nomchamo isuka ku-5% iye ku-60%.35 Ucwaningo luka-Johan lubonise ukuthi i-ctDNA yokuguqulwa kwe-spectrum ekupheleni kwe-HCC inezinga lokuguqulwa elifanayo ku-HCC yakuqala, okuhlanganisa umgqugquzeli we-TERT (51%), TP53 (32%), CTNNB1 (17%), PTEN (8%), ukuguqulwa I-AXIN1 ., ARID2, KMT2D kanye ne-TSC2 (6% ngayinye).36 I-β-catenin (CTNNB1) i-oncogene idlala indima ebalulekile endleleni yokusayina ye-Wnt.I-coactivator yokubhala i-CTNNB1 ingaphromotha ukusho kofuzo, okungaholela ekwandeni kwamaseli, ukuvinjwa kwe-apoptosis, kanye ne-angiogenesis.I-CTNNB1 ingaphinde ihlanganyele ne-TERT ukuze yenze ukuguqulwa kwe-hepatocyte.33 Umgqugquzeli we-TERT uvame ukuguqulwa kwezinye izimila eziqinile.Izinguquko ku-TERT, olunye lwezinguquko zokuqala zofuzo ekuguqulweni okubi kwe-HCC, zingase ziholele ekwenziweni kabusha kwe-telomerase kuma-hepatocyte e-cirrhotic futhi kungase kukhuthaze ukwanda futhi kuvimbele ukuguga.Ukuguqulwa kwezinguquko kumgqugquzeli we-33-37 TERT kubikwe ukuthi kwenzeka ku-59-90% weziguli ezinamaqhuqhuva esibindi akhulayo kanye ne-HCC yakuqala futhi kuhlotshaniswa nokusinda.38
Izinguquko zenombolo yekhophi (CNA) ziwuhlobo oluncane olubalulekile lwezinguquko ze-somatic.Ucwaningo luye lwabonisa ukuthi umthwalo osabalele futhi ogxile we-CNA uyisiginesha ye-genomic ekwazi ukubikezela ukungena kwe-tumor immune kanye nokukhishwa kwezinye izinhlobo zomdlavuza.39 Isignali yokungena esebenzayo, umsebenzi ophezulu we-cytolytic, ukuvuvukala okukhulu kanye nezimpawu zofuzo ezihlobene nokwethulwa kwe-antigen ku-HCC.Ukuhlaziywa kohlu lwedatha ye-nucleotide polymorphisms eyodwa ezifundweni ezingama-477 kwembule umthwalo ophansi ku-CNS.Ngokuphambene, izimila ezingazinzile ze-chromosomal ezinomthwalo omkhulu obanzi we-CNA zibonise izimpawu zokwenqatshwa kwamasosha omzimba futhi zazihlotshaniswa nokwanda, ukulungiswa kwe-DNA, kanye nokungasebenzi kahle kwe-TP53.Xu et al.ibonise ukuthi iqembu le-HCC lalinamaphuzu aphezulu e-CNA kuneqembu lesifo sesibindi esingamahlalakhona.40 Kusetshenziswa ukulandelana kofuzo oluphelele lweseli eyodwa, ama-CNA atholwe avela kusenesikhathi ku-hepatocarcinogenesis futhi ahlala ezinzile ngesikhathi sokukhula kwesimila.41 Chung et al.ithole ukuthi amazinga e-cfDNA anyuswe kakhulu ezigulini ze-HCC nokuthi ama-CNA e-genome-wide ku-cfDNA ayewumaka obalulekile ozimele wokubikezela ezigulini ze-HCC ezelashwa nge-sorafenib.Iziguli ezingama-42 ezinomthwalo ophakeme we-CNA zazingase zibe nokuqhubekela phambili kwezifo nokufa kunalezo ezinomthwalo ophansi we-CNA.U-Ollerich et al.ithole ukuthi inkomba yokungaqini kwenombolo yekhophi (CNI) ingasetshenziswa ukuhlola i-CNA ku-cfDNA yeziguli ezinomdlavuza.Baphawule ukuthi iziguli ezinomdlavuza othuthukile zinamaphuzu e-CNI aphezulu kakhulu kuneqembu elilawulayo, elihlola impendulo yesiguli ku-systemic chemotherapy kanye ne-immunotherapy.43 Le miphumela iphakamisa ukuthi ama-CNA atholakala kumasampula e-liquid biopsy angase asebenze njengezinkomba zokubikezela ezigulini ezinomdlavuza osezingeni eliphezulu.I-HCC ngemuva kwe-systemic therapy.
Njengamanje, izindlela ezisetshenziswayo ukuthola i-ctDNA zingahlukaniswa zibe izindlela ezihlosiwe nezingahlosiwe.Kafushane, izindlela ezihlosiwe ezifana ne-digital polymerase chain reaction (dPCR), BEAMing digital PCR, Amplification Refractory Mutation System-PCR, Capp-Seq kanye ne-Tam-Seq zizwela kakhulu ezakhini zofuzo ezichazwe ngaphambilini.Izindlela ezingezona eziqondiwe ezifana nokulandelana kofuzo lonke kanye ne-NGS zinikeza umbono obanzi wayo yonke i-genomic landscape.44 Uma kuqhathaniswa namaphaneli okuqondiwe, ukulandelana kofuzo lonke akukwazi nje ukubona ukuguqulwa kwamaphoyinti nokufakwayo, kodwa futhi nokuhlela kabusha nokuhlukahluka kwezinombolo.ukubikezela, kanye ne-CTC kanye ne-cfDNA yizinkomba ezinhle ezingasetshenziselwa ukuqapha okuguquguqukayo kwe-HCC.45 Ngaphezu kwalokho, ukuhlaziywa kwe-cfDNA kungase kube usizo kakhulu ekutholeni i-HCC.Yan et al.ibonise ukuthi i-cfDNA ku-plasma yeziguli ezine-HCC yayiphezulu kakhulu kuneziguli ezine-fibrosis yesibindi nezilawuli ezinempilo.Uma kuqhathaniswa ne-AFP, i-ctDNA kulindeleke ukuthi ibe umaka ongcono wokuhlola we-HCC yakuqala.46 Ocwaningweni oluzoba khona lwama-biopsy oketshezi angama-47 ahlole i-cfDNA kanye namaprotheni esixukwini sabantu, aboniswe esebenza ngempumelelo ekwehlukaniseni iziguli ezine-HCC ezigulini ezingenayo i-HCC.Ekulandeleni iziguli ezingama-331 ze-ultrasound ezijwayelekile nezingenayo i-AFP, ukuzwela nokucaciswa kwe-cfDNA ekuxilongeni i-HCC kwakungu-100% no-94%, ngokulandelana, ukuze i-cDNA ikwazi ukubona i-HCC kubantu abangenazimpawu ze-HBsAg abane-seropositive.Ocwaningweni lwe-Yeo48, imvamisa ephezulu (92.5%) ye-hypermethylation yomgqugquzeli we-RASSF1A itholwe ezigulini ezine-HCC.Ngaphezu kwalokho, uXu et al.idale imodeli yokuxilonga ukuze ibikezele i-HCC isebenzisa iphaneli yezimpawu ezithile ze-methylation ezinemininingwane nokuzwela okungu-90.5% no-83.3%, ngokulandelana.Iphaneli ivumela iziguli ezine-HCC ukuba zihlukaniswe ezigulini ezinezinye izifo zesibindi, okungcono kune-AFP.Baphinde bathola ukuthi izilawuli ezijwayelekile ezitholakale zine-HIV zingase zibe nezici engcupheni ye-HCC, njengokutheleleka nge-HBV noma umlando wokusetshenziswa kotshwala.25 Sicabanga ukuthi izici eziyingozi kakhulu ze-HCC zingase zikhuthaze i-hypermethylation ye-cfDNA, ebese ibe nomthelela ekuqhubekeleni phambili kwe-HCC, futhi ngaleyo ndlela i-cfDNA ingase idlale indima ebalulekile ekuhloleni amaqembu asengozini enkulu.Cai et al.fingqa uhla olugcwele lokuguqulwa kwe-ctDNA futhi unikeze isu eliqinile lokuhlola umthwalo wesimila ezigulini.49 Leli su lingakwazi ukubona i-tumorigenesis eyi-median yezinyanga ezingu-4.6 ngaphambi koshintsho lwesithombe futhi ibonise ukusebenza kokuxilonga okuphakeme uma kuqhathaniswa nama-serum biomarkers AFP, AFP-L3, kanye ne-PIVKA-II.Inani lokuxilonga lokuhlolwa kwe-cDNA liye laboniswa lapho ukuhlolwa kwesithombe kungatholakali, ngakho ukuhlolwa kwe-cDNA kunenani ekuxilongweni kwe-HCC yakuqala emaqenjini asengozini enkulu.Muva nje, ososayensi basebenzise ubuchwepheshe be-NGS ukuhlaziya izinkomba zokuhlukahluka kofuzo okuhlukahlukene (okuhlanganisa i-5-hydroxymethylcytosine, 5′-motif, ukuhlukaniswa, i-nucleosome trace, i-HIFI) kumasampula omtholampilo angu-3204 kanye ne-cfDNA.Amamodeli e-HIFI aqinisekiswe kabusha angama-50 anesitimela esizimele amathathu, amasethi okuhlola, namasethi okuhlola abonise ukucwasa okuzinzile nokwethembekile phakathi kwe-HCC nabantu abangewona abe-HCC abanokuzwela okungu-95.79% no-95.42% kumasethi okuhlola aqondene ne-HCC, ngokulandelana.Ubulili bebungu-95.00% no-97.83%, ngokulandelana.Inani lokuxilonga lendlela ye-HIFI lingaphezulu kwele-AFP ekuhlukaniseni i-HCC ne-cirrhosis.Ngaphezu kwalokho, i-ctDNA nayo isetshenziswa ekwelashweni kokuhlinzwa.Atsushi et al.inqume amazinga e-serum yangaphambi kokuhlinzwa ye-ctDNA ezigulini ezine-HCC futhi yathola ukuthi izinga lokuphindaphinda kanye nezinga le-extrahepatic metastasis eqenjini elihle le-cDNA laliphezulu kakhulu kuneqembu elingalungile le-cDNA, futhi amazinga e-cDNA ayehlotshaniswa kakhulu.nokuqhubeka kwesimila.51 Njengoba iyi-biomarker ezwela kakhulu, i-ctDNA ingabikezela ikhono le-HCC lokuhlasela imikhumbi.Wang et al.yenza ukulandelana kofuzo okuphelele kweziguli ezingama-46 ezine-HCC, futhi ukuhlaziywa kwe-multivariate kubonise ukuthi inani lomkhawulo we-allele frequency ye-cDNA ehlukile yokuhlasela kuma-microvessels ngu-0.83%, ukuzwela okungu-89.7% kanye nokucaciswa okungu-80.0%.isici esizimele esiyingozi sokuhlasela kwe-microvascular ku-HCC ekhishwa kabusha, ephakamisa ukuthi i-cDNA ingasiza ukuqondisa ukwelashwa okufanele.Sengiphetha, i-ctDNA ibandakanyeka ngokugcwele ekwenzekeni nasekuthuthukisweni kwe-HCC futhi ingasetshenziselwa ukuhlola kusenesikhathi, ukuhlola ngokuhlinzwa, nokuqapha izifo.
Ama-CTC amangqamuzana abulalayo atholakala kumathumba ayinhloko noma ama-metastases angena egazini.Amaseli e-tumor akhiqiza i-matrix metalloproteinases (MMPs), ephula ulwelwesi olungaphansi, okuvumela amangqamuzana e-tumor ukuthi angene ngqo egazini kanye nemithambo ye-lymph.Kodwa-ke, ama-CTC amaningi aqedwa ngokushesha yi-anoikis, ukuhlasela kwamasosha omzimba, noma ukucindezeleka kwe-shear.53 I-epithelial-mesenchymal transition (EMT) ivumela ama-CTC ukuthi ahlukaniswe kalula nezicubu zesimila esiyinhloko, ahlasele ama-capillaries, futhi athole ukuphila okuthuthuke kakhulu, imetastasis, invasiveness, kanye nokumelana nezidakamizwa.Ucwaningo luye lwabonisa ukuthi kukhona ukuhlukahluka okujulile phakathi kwamaseli e-tumor ahlukahlukene kuma-primary metastatic tumors.Ngakho-ke, ukuhlaziywa kwe-CTC kungaholela ekuqondeni okuphelele kwe-tumor cell heterogeneity.54
Omaka abathile bama-CTC ahlotshaniswa ne-HCC bahlanganisa i-glypican-3 (GPC3), i-asialoglycoprotein receptor (ASGPR), i-epithelial cell adhesion molecule (EpCAM) kanye nomaka be-stem cell-associated njenge-CD44, CD90, 55 kanye ne-intercellular adhesion molecule 1 (ICAM1).) .56 Umaka we-GPC3 iphrotheni ebambelele kulwelwesi lweseli esetshenziswa ngokomtholampilo ukuze kuhlaziywe ukugula nokuhlukanisa i-HCC.57 Ukuvezwa kwe-GPC3 kuvame kakhulu kumaseli e-HCC wesimila anokwahlukana okuphakathi nendawo okuphansi futhi kukhuthaze ukufuduka kwe-extrahepatic;ngaphezu kwalokho, ukuba khona kwe-GPC3+ CTCs kubonisa i-HCC ye-metastatic.I-58 ASGPR iphrotheni ye-transmembrane evezwa kuphela ebusweni be-hepatocyte futhi ibonakaliswa kakhulu nge-HCC ehluke kahle.I-EpCAM ingelinye lamaprotheni asetshenziswa kakhulu ulwelwesi ukuze kuthwebule ama-CTC.I-EpCAM ikhonjwe njengophawu olungaphezulu lwamaseli e-HCC anezici ze-stem cell, i-59 ehambisana nezici ezihlukahlukene ze-clinicopathological ze-HCC, njengokuhlasela kwemithambo, amazinga e-AFP ahlolwe, kanye nesigaba esithuthukisiwe somdlavuza wesibindi e-Barcelona Hospital (BCLC).I-phenotype engu-60 CTC EMT ine-metastatic kakhulu.Izinqubo ezingama-54 ze-EMT ku-CTC zithuthukisa imetastasis ye-HCC.Ukuvezwa komaka be-EMT njenge-vimentin, twist, E-box zinc finger binding (ZEB) 1, ZEB2, umnenke, slug, ne-E-cadherin kuye kwacwaningwa kuma-CTC asuselwe esibindini ezigulini ze-HCC.58 Uhlelo lwe-CanPatrol™ olwakhiwe u-Cheng [61] luhlukanise ama-CTC aba ama-subgroups amathathu e-phenotypic asekelwe kumaka avezwa kakhulu: i-epithelial phenotype (EpCAM, CK8/18/19), i-mesenchymal phenotype (i-vimentin, i-coiled), nama-phenotypes axubile.Ezigulini eziyi-176, i-CTC isiyonke yayiphakeme kune-AFP ekuhlukaniseni i-HCC nesifo sesibindi esiyingozi.Amanani e-AUC engqikithi ye-CTC, i-AFP, kanye nengqikithi ehlanganisiwe ye-CTC ne-AFP abengu-0.774 (95% CI, 0.704–0.834), 0.669 (95% CI, 0.587–0.750), kanye no-0.821 (95% CI, 0.886–0.786) ).), ngokulandelana.Ukuhlukaniswa kwe-CTC okusekelwe ku-EMT kungabikezela ukuxilongwa kwe-HCC, ukuvela kabusha kwangaphambi kwesikhathi, ukutholakala kwe-metastasis, kanye nesikhathi esifushane.
Njengamanje, izindlela zokuthola ama-CSC zifaka izindlela ezingokwenyama kanye nezindlela zebhayoloji.Izindlela ezibonakalayo, ezivame ukubizwa ngokuthi ukunothisa okusekelwe ezintweni eziphilayo, zincike kakhulu ezintweni ezibonakalayo ze-CSC, njengosayizi, ukuminyana, ukushaja, ukuhamba kanye nokukhubazeka.Kuye ngezakhiwo ezibonakalayo, kunezindlela ezihlukahlukene ezifana nezinhlelo ezisekelwe ku-filtration, i-dielectrophoresis, njll. Le yokugcina, eyaziwa nangokuthi i-immunoaffinity-based enrichment, isekelwe ikakhulukazi ekubopheni ama-antigen-antibody njengoba le ndlela isebenzisa amasosha omzimba ngokumelene nama-biomarker aqondene nesimila. njenge-EpCAM, ASGPR, human epidermal growth factor receptor 2 (HER2), prostate specific antigen (PSA), human pancytokeratin (P-CK) kanye ne-carbamoyl phosphate synthase 1 (CPS1).62 Olunye uhlobo, olubizwa ngokuthi indlela yokungacebisi, lusebenzisa i-flow cytometry ukuze luhlukanise ama-CTC kumaleukocyte ngokusekelwe esilinganisweni esiphezulu senuclear-to-cytoplasmic kanye nosayizi.Okwamanje, ukuphela kokuhlolwa okugunyazwe i-FDA kokutholwa kwama-CTC uhlelo lwe-Cell-Search™, olusebenzisa umaka we-EpCAM cell surface. Nokho, ukutholwa kwe-CTC okusekelwe kumaka okuhlanganisiwe kungase kwenyuse izinga le-positivity.54 Ingxubevange yamasosha omzimba ngokumelene ne-ASGPR ne-CPS1 izuze izinga lokutholwa kwe-CTC lika-91% ezigulini ze-HCC.63 UZhang et al wasebenzisa i-CTC-Chip enamasosha omzimba alwa ne-ASGPR, P. -CK kanye ne-CPS1, futhi yahlukanisa iziguli ze-HCC kulabo abanesifo sesibindi esiyingozi noma umdlavuza ongewona we-HCC ngenani lika-100%.64 Ucwaningo olwenziwa ngu-Wang luthole ama-EpCAM+ CTCs ku-60% yeziguli ze-42 HCC futhi lwathola ukuhlobana okubalulekile phakathi kokubili kokuhle isilinganiso kanye nenani lama-CTC anesiteji se-TNM.65 Guo et al bathole ukuthi amaphuzu e-PCR atholakala ku-CTC anyuswe ezigulini eziyi-125/171 (73%) ezizinga le-AFP lalingu-<20 ng/mL nokuzwela okungu-72.5% kanye ukucaciswa okungu-95.0%, uma kuqhathaniswa no-57.0% no-90.0% we-AFP ekunqamuleni okungu-20 ng/mL.66 Inhlanganisela ye-AFP ne-CTC ingase ithuthukise ukutholwa kwe-HCC.45 Kukholakala ukuthi ama-CTC anenzuzo kune-AFP ekuhlolweni kwamaqembu kwangaphambi kwesikhathi. engozini enkulu ye-HCC. Nokho, ukutholwa kwe-CTC okusekelwe kumaka okuhlanganisiwe kungase kwenyuse izinga le-positivity.54 Ingxubevange yamasosha omzimba ngokumelene ne-ASGPR ne-CPS1 izuze izinga lokutholwa kwe-CTC lika-91% ezigulini ze-HCC.63 UZhang et al wasebenzisa i-CTC-Chip enamasosha omzimba alwa ne-ASGPR, P. -CK kanye ne-CPS1, futhi yahlukanisa iziguli ze-HCC kulabo abanesifo sesibindi esiyingozi noma umdlavuza ongewona we-HCC ngenani lika-100%.64 Ucwaningo olwenziwa ngu-Wang luthole ama-EpCAM+ CTCs ku-60% yeziguli ze-42 HCC futhi lwathola ukuhlobana okubalulekile phakathi kokubili kokuhle isilinganiso kanye nenani lama-CTC anesiteji se-TNM.65 Guo et al bathole ukuthi amaphuzu e-PCR atholakala ku-CTC anyuswe ezigulini eziyi-125/171 (73%) ezizinga le-AFP lalingu-<20 ng/mL nokuzwela okungu-72.5% kanye ukucaciswa okungu-95.0%, uma kuqhathaniswa no-57.0% no-90.0% we-AFP ekunqamuleni okungu-20 ng/mL.66 Inhlanganisela ye-AFP ne-CTC ingase ithuthukise ukutholwa kwe-HCC.45 Kukholakala ukuthi ama-CTC anenzuzo kune-AFP ekuhlolweni kwamaqembu kwangaphambi kwesikhathi. engozini enkulu ye-HCC.Kodwa-ke, ukutholwa okuhlanganisiwe okusekelwe kumaka kungase kwandise iphesenti lemiphumela emihle.54 Ingxubevange yama-anti-ASGPR kanye nama-CPS1 amasosha omzimba azuze izinga lokutholwa kwe-CTC lama-91% ezigulini ezine-HCC.63 Zhang et al.wasebenzisa i-CTC-Chip enamasosha omzimba alwa ne-ASGPR, i-P-CK ne-CPS1, futhi wahlukanisa iziguli ezine-HCC kulezo ezinesifo sesibindi esiyingozi noma okungezona i-HCC ngenani elingu-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 i-групп. imvamisa kanye nenani lama-CTC anesiteji se-TNM.65 U-Guo et al uthole ukuthi i-PCR etholakala kuma-CTC yaphakanyiswa ezigulini eziyi-125/171 (73%) ezazinamazinga e-AFP <20 ng/mL ngokuzwela kwe-72.5% kanye nokucaciswa kwe U-95.0% uma kuqhathaniswa no-57.0% no-90.0% we-AFP ezingeni elinqunyiwe lika-20 ng/mL.66 Inhlanganisela ye-AFP ne-CTC ingase ithuthukise ukutholwa kwe-HCC.45 CTCs ibhekwa njengenzuzo kune-AFP ekuhlolweni kusenesikhathi. amaqembu.ngengozi enkulu ye-HCC.Nokho, ukutholwa okuhlanganisiwe okusekelwe kumaka kwama-CTC kungase kwenyuse iphesenti lemiphumela emihle.54 Ingxubevange yamasosha omzimba alwa ne-ASGPR kanye ne-CPS1 izuze izinga lokutholwa kwe-CTC elingu-91% ezigulini ezine-HCC.63 Zhang et al.isebenzise ama-CTC chips anamasosha omzimba alwa ne-ASGPR, i-P-CK ne-CPS1 futhi yahlukanisa iziguli ezine-HCC kusukela ezifweni zesibindi ezingenabungozi kanye ne-non-HCC ene-100%.Ucwaningo luka-64 Wang luhlonze u-60% we-EpCAM+ CTC ezigulini ezingama-42 HCC futhi lwathola ukuhlobana okubalulekile phakathi kwesigameko nenani lama-CTC esigabeni se-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 为 pcr 评分 升高, ctc 为 为 72.5%, 而 为 95.0%, 而 为 95.0%, 而 为 95.0%值为20 ng/mL 时的特异性為57.0% 和90.0%. 65 Guo 等 人 发现 在 在 在 水平 <ng / ml 的 125/171 (73%) 名 患者 ,, ctc 衍生 pcr 评分, 为 为 为 72.5%, afp 在 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. bathole ukuthi ku-125/171 (73%) iziguli ezinamazinga e-AFP <20 ng/mL, amanani e-PCR asuselwa ku-CTC akhushulwe ngokuzwela okungama-72.5% nokucaciswa okungu-95.0%, kuyilapho i-AFP yayisesimweni esinqunyiwe. kwakungu-20 ng/mL.ml yayingu-57.0% no-90.0%.66 Inhlanganisela ye-ORP ne-CTC ithuthukisa ukutholwa kwe-HCC.Ama-CTC angu-45 kucatshangwa ukuthi aphakeme kune-AFP ekuhlolweni kwangaphambi kwesikhathi kwezibalo ze-HCC ezisengozini enkulu.Ngakho, emaqenjini e-CTC-positive kanye nanobungozi obukhulu be-HCC, ukuhlolwa kwe-CTC kufanele kuhlanganiswe njalo nokutholwa kwe-ultrasound kanye ne-AFP.Kodwa-ke, ama-CTC abhekwa njengezibikezelo ezibalulekile ze-tumor metastasis nokuphinda, futhi ukutholwa kwama-CTC akunconyiwe ngokuzimela njengethuluzi lokuxilonga.62 Ngakho-ke, i-CTC ingase isebenze njengesibikezelo sezinto eziphilayo esingcono kunabanye omaka abasetshenziswa njengamanje. U-Zhou et al uthole ukuthi iziguli ezinezinombolo eziphakeme ze-EpCAM + CTCs kanye namaseli e-T alawulayo abonisa ingozi enkulu yokuthuthukisa ukuphindaphinda kwe-HCC, kunalabo abanezinombolo eziphansi ze-CTCs, ngesilinganiso sokuphindaphinda kwe-66.7% vs 10.3% (P <0.001) .67 Ucwaningo olufanayo lwabikwa nguZhong et al.68 Ngaphezu kwalokho, u-Qi wathola ukuthi iziguli ezingu-101 kwezingu-112 (90.81%) ezine-HCC, kuhlanganise nalabo abanesifo sesigaba sokuqala, zazilungile kuma-CTCs nokuthi ama-nodule amancane kakhulu e-HCC atholwe ngemva kwe-3. kuya ezinyangeni ezi-5 zokulandelela. U-Zhou et al uthole ukuthi iziguli ezinezinombolo eziphakeme ze-EpCAM + CTCs kanye namaseli e-T alawulayo abonisa ingozi enkulu yokuthuthukisa ukuphindaphinda kwe-HCC kunalezo ezinezinombolo eziphansi ze-CTCs, ngesilinganiso sokuphindaphinda kwe-66.7% vs 10.3% (P <0.001) .67 A Ucwaningo olufanayo lwabikwa nguZhong et al.68 Ngaphezu kwalokho, u-Qi wathola ukuthi iziguli ezingu-101 kwezingu-112 (90.81%) ezine-HCC, kuhlanganise nalezo ezinesifo sokuqala, zazilungile kuma-CTCs nokuthi ama-nodule e-HCC amancane kakhulu atholwe ngemva kwe-3 kuya. Izinyanga ezi-5 zokulandelela. Чжоу futhi 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 uthole ukuthi iziguli ezine-EpCAM + CTCs eziphakeme kanye namaseli e-T alawulayo zinengozi enkulu yokuphindaphinda kwe-HCC kunalawo ane-CTC ephansi, enezinga lokuphindaphinda le-66.7% vs 10.3% (P<0.001)67.Ucwaningo olufanayo lwenziwa nguZhong et al.68. Ukwengeza, i-Qi ithole ukuthi iziguli eziyi-101 kweziyi-112 (90.81%) ezine-HCC, kuhlanganise nalezo ezinesifo sangaphambi kwesikhathi, zinama-CTC, nokuthi ama-nodule e-HCC amancane kakhulu atholwe ngemva kwezinyanga ezi-3 kuya kwezingu-5 zokulandelela. Zhou 等 人 发现, 与 CTC 数量 较 少少 Zhou 等等 发现 与与 CTC 数量 的 患者 患者 患者 患者 患者 相比 相比, EPCAM + CTC 和 T 上 细胞数量 患者的患者 HCC 复发的 为为更, 复发率复发率 为为更, 为复发率 为为 为为 为为 为为 为 为为p <0.001)........... Чжоу futhi 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). UZhou et al.bathole ukuthi iziguli ezine-EpCAM + CTCs eziphakeme kanye namaseli e-T alawulayo zinengozi enkulu yokuphindaphinda kwe-HCC uma kuqhathaniswa neziguli ezine-CTC ezimbalwa, nezinga lokuphindaphinda kwe-66.7% ne-10.3%, ngokulandelana (P <0.001).Ucwaningo olufanayo lwabikwa nguZhong et al.68 Ngaphezu kwalokho, i-Qi ithole ukuthi iziguli eziyi-101 kweziyi-112 ze-HCC (90.81%), okuhlanganisa neziguli ezinesifo sangaphambi kwesikhathi, zinemiphumela emihle ye-CTC futhi zithole ama-nodule e-HCC amancane kakhulu ngemva kokuvakasha kuka-3.Ukubuka kufika ezinyangeni ezi-5.Baphinde bathola ama-CTC ezigulini eziyi-12 ezinokutheleleka okungapheli kwe-HBV futhi bathola izimila ezincane ze-HCC phakathi nezinyanga ezi-5 ezigulini ezi-2 ezine-CTC.69 Ngakho-ke, ama-CTC angasetshenziswa ukubikezela i-HCC, 70 kodwa angasetshenziswa ngokujwayelekile njengama-biomarker aqagelayo.
Njenge-cfDNA, i-cfRNA ikhishelwa egazini ngamasistimu ahlukahlukene.Lawa ma-athomu egazini le-peripheral amelela izicubu ezinomdlavuza wemvelaphi.Uma kuqhathaniswa nezimpawu ezitholwe ngezindlela ezingahlaseli, ama-cfRNA alawulwa ngamandla, aqondene ngqo nezicubu, futhi maningi endaweni engaphandle kwamaseli.Ukubaluleka kanye nenani lokuxilonga lama-71 miRNAs (miRNAs) ku-HCC kubikwe ezifundweni eziningi.Ama-miRNA angama-RNA angafaki ikhodi endogenous (ncRNAs) alawula imisebenzi ehlukahlukene yamangqamuzana ebhayoloji ngokuvimbela ukuhunyushwa kwe-target messenger RNAs (mRNAs).Ama-miRNA atholakala emizimbeni ye-apoptotic embozwe kuma-exosomes, kodwa angaphinde abophe ngokuzinzile kumaprotheni e-serum nama-lipids egazini le-peripheral futhi angasetshenziswa ukuhlola i-HCC.Ama-microRNA abandakanyeka ekuvuseleleni isibindi, i-lipid metabolism, i-apoptosis, ukuvuvukala, kanye nokuthuthukiswa kwe-HCC.72 Ama-Oncogenic miRNA afana ne-miR-21, miR-155 kanye ne-miR-221 aziwa kakhulu ku-HCC.Ikakhulukazi, i-miR-21 idlala indima ebalulekile ekuhlanganiseni kwe-collagen ku-matrix ye-extracellular kanye ne-fibrosis futhi ikhuthaza i-hepatocarcinogenesis ngokwenza kusebenze amaseli e-hematopoietic stem.I-72,73 Tumor suppressor miRNAs ku-HCC ihlanganisa i-miRNA-122, miRNA-29, umndeni wakwa-Let-7, kanye nomndeni we-miRNA-15.Umndeni wakwa-Let-7 uqukethe ama-miRNA amaningi acindezela isimila aqondise umndeni wakwa-RAS.Umndeni we-miR-15 uhlanganisa i-miR-15a, i-miR-15b, i-miR-16, i-miR-195, ne-miR-497, ezinokulandelana okuhambisanayo kwama-mRNA athile.Ukwengeza, ama-RNA amade angafaki ikhodi (lncRNAs) kanye nama-RNA ayindilinga (cirRNAs) nawo abalulekile ekuhlolweni kusenesikhathi kwe-HCC.Ama-lncRNA amele isigaba esibanzi kakhulu sama-ncRNA, kufaka phakathi ama-ncRNA afana ne-mRNA, futhi ahileleke ku-pathogenesis yezifo eziningi zabantu.I-LncRNAs idlala indima yokulawula ku-microenvironment yesibindi kanye nesifo sesibindi esingamahlalakhona.I-74 CircRNAs futhi iyisigaba sama-ncRNA anemisebenzi eminingi ekulawuleni ukuvezwa kofuzo.Muva nje, ama-circRNA athathwe njengamathuluzi okuxilonga e-HCC.
I-RNA yamahhala ejikelezayo inokusimama okumangalisayo, okuhlanganisa ukumelana nezinga lokushisa, i-pH, ne-RNase, okwenza ukuhlukaniswa kwe-fnRNA egazini le-peripheral kungabi nesicefe kusetshenziswa izindlela ezijwayelekile zokuhlanza i-RNA.Izindlela ezisetshenziswa kakhulu zihlanganisa i-NGS, i-microarray kanye ne-RT-qPCR.I-NGS ivumela ama-microRNAs ukuthi akalwe kulo lonke i-genome.Nokho, le ndlela iyabiza futhi ukuhlaziya akujwayelekile.Ngokuphambene, i-RT-qPCR ayibizi, ikhulisa ngokushesha ama-nucleic acid, futhi inikeza izinzuzo eziningi njengokuzwela okuphezulu, ukunemba okuphezulu, ububanzi obuguquguqukayo obubanzi, futhi idinga amasampula ambalwa.Ama-Microarrays angenye indlela esetshenziselwa ukutholwa kwe-miRNA esekelwe ekuhlanganiseni okubucayi nokuqondile kwama-miRNA aqondiwe nama-DNA probes ahambisanayo, 75 kodwa ukuhlaziya idatha ye-microarray kudla isikhathi.
Ukujikeleza i-miR-122 kanye ne-Let-7 kubikwe njengokungaba wusizo ekuxilongeni i-HCC yesigaba sangaphambi kwesikhathi emaqenjini asengozini enkulu, omaka ezigulini ezinamaqhuqhuva ahlobene ne-HBV kanye ne-HCC yesigaba sangaphambi kwesikhathi.76 Cai et al.ithole ukuthi amalungu omndeni wakwa-Let-7 (miR-92, miR-122, miR-125b, miR-143, miR-192, miR-16, miR-126, kanye ne-miR-199a/b) asengozini yokugula okungapheli. HCC ezigulini ezine-hepatitis.Umndeni wakwa-Let-7 ungasebenza njenge-biomarker ye-surrogate ephumelelayo yokubikezela ukuthuthukiswa kwe-HCC emaqenjini asengozini enkulu ahlobene ne-hepatitis C engapheli. I-77 miR-122 inokunemba okuphezulu kokuxilonga ekutholeni i-HCC yokuqala ezigulini ezinesifo sokusha kwesibindi.I-78 Serum ejikeleza i-MiR-107 nayo iye yahlolwa ezigabeni zokuqala ze-HCC, 79 futhi ibonise amandla amahle kubantu abasengozini enkulu.UZhou et al ubike ukuthi iphaneli ye-miRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a kanye ne-miR-801) ingahlukanisa i-HCC ku-hepatitis B (CHB) engapheli kanye ne-cirrhosis. ukuzwela kwaba ngu-79.1% no-75%, kanye nokucaciswa okungu-76.4% no-91.1%, ngokulandelana.80 Ku-HCC ehlobene ne-HBV, sithole ukuthi amazinga e-miR150 ehle kakhulu uma kuqhathaniswa nalawo ezigulini ze-HBV ezingamahlalakhona ezingenayo i-HCC (ukuzwela okungu-79.1%, ukucaciswa okungu-76.5%).-224 yaphakanyiswa ku-HCC uma kuqhathaniswa nokulawula okunempilo, futhi ukuhlaziya kweqembu elincane kubonise amazinga aphezulu ezigulini ezine-HCC ezihambisana ne-HBV.i-hepatitis B ehambisana ne-cirrhosis kanye neziguli ze-HCC zihlonze isigaba se-siRNA esiqukethe ama-siRNA ayisikhombisa avezwe ngokwehlukana angakwazi ukubona i-HCC ezilawulweni ezahlukene;Ibanga le-AUC ekuhlolweni kusenesikhathi lingcono kunamavolontiya e-AFP.Bathole ukuthi ama-miRNA amane (miR-1972, miR-193a-5p, miR-214-3p, kanye ne-miR-365a-3p) akwazi ukuhlukanisa iziguli ezine-HCC ezigulini ezingenayo i-HCC.Ama-miRNA amahlanu aveza ngokweqile (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p, kanye ne-miR-148a-3p) abhekwa njengezifo ezingenzeka ze-HBV ku-HCC, i-cirrhosis, ne-CHB biomarkers, ikakhulukazi. I-miR-34a-5p ingase ibe ama-biomarker we-cirrhosis yesibindi,85 futhi ingase ibe ama-biomarker angaba khona ekuhlolweni kokuqala kwe-HCC kubantu abasengozini enkulu.I-lncRNA efundwe kakhulu ku-HCC yenziwe yasebenza kakhulu kumdlavuza wesibindi (HULC).Olunye ucwaningo luye lwabonisa ukuthi i-HULC ejikeleza ezigulini ze-HCC ingasetshenziswa njengomaka wokuxilonga ngoba le lncRNA ilawulwa kakhulu ezigulini ze-HCC uma kuqhathaniswa nabantu abanempilo.71,86 Phakathi kwamanye ama-lnRNA, i-LINC00152 ibhekwa njenge-lncRNA engcono kakhulu yokuxilonga ngenxa ye-AUC ephezulu, ukuzwela kanye nokucaciswa kwayo.86 Kolunye ucwaningo, ukubonakaliswa kwegazi okujikelezayo kwe-LINC00152 kancane kancane kwanda kusuka ekulawuleni okujwayelekile okunempilo kuya ezigulini ezine-CHB kanye ne-cirrhosis, futhi ekugcineni kwaba okuphezulu ku-HCC.Ucwaningo lokuvezwa kwe-circSMARCA5 ku-plasma yeziguli ezine-HCC lubonise ukwehla okuqhubekayo ekukhulumeni kwe-HCC kusukela ku-hepatitis kuya ku-cirrhosis kanye nezilonda ezinomdlavuza.87 Ukuhlaziywa kwamajika e-ROC kuqinisekise amandla alawa ma-circRNA ekuhlukaniseni iziguli ezine-hepatitis noma i-cirrhosis yesibindi kulabo abane-HCC, ikakhulukazi lezo ezinamazinga e-AFP angaphansi kuka-200 ng/mL.Ukwengeza, u-Zhu uhlaziye ama-RNA angu-13,617 kumasampula e-plasma avela ezigulini ze-HBV ezihlotshaniswa ne-HBV futhi waqinisekisa ukuthi ama-RNA angu-6 wama-cyclic avezwe ngendlela ehlukile ku-HCC kanye ne-cirrhosis ehlobene ne-HBV, ephakamisa ukuthi ama-cRNA angase abe nenzuzo.izimpawu zokuhlolwa kusenesikhathi kwamaqembu asengozini enkulu njengalawo ahlotshaniswa nesifo sesibindi, iziguli ze-sclerosis.88
Ama-exosomes ama-membrane vesicles 40-160 nm ububanzi;ama-vesicle amaningi e-intracellular ahlangana nolwelwesi lweseli futhi adedelwa ku-matrix engaphandle kweseli.Aqukethe izakhi eziningi ezisebenzayo, okuhlanganisa ama-lipids, amaprotheni, i-RNA ne-DNA, futhi adlala indima ebalulekile ekuxhumaneni phakathi kwamaseli, womabili amaseli e-HCC nama-non-HCC.I-89,90 Exosomes ilawula ukuqhubeka kwe-HCC ngokwenza kusebenze i-hepatocyte fibroblasts namaseli e-stellate, amaseli omzimba, ama-hepatocyte avamile, namaseli e-HCC.91 Ku-tumor microenvironment, amaseli wesimila akhiqiza inqwaba yama-exosomes athwalwa esuka kumangqamuzana omdlavuza aye kumaseli angakavuthwa, nawo abandakanyeke ku-oncogenesis, ukuwohloka, kanye nokusayina kwamaselula.92 Ucwaningo luye lwabonisa ukuthi ama-exosomes angadlulisela ama-oncogenes kumaseli avamile phakathi nezinqubo ze-pathological, okungenzeka kube enye yezindlela zokuhlasela kwesimila kanye ne-metastasis.93 Indima yama-exosomes ekuqhubekeleni phambili komdlavuza ingase ibe namandla futhi iqonde uhlobo lomdlavuza, i-89 Exosomes ingase ifakwe ngaphakathi ngamaseli aseduze noma akude ukuze alawule izakhi zofuzo eziningi ezihlosiwe kumaseli owamukelayo angase ahileleke kuma-ion okuxhumana phakathi kwamaselula kanye nokusebenzisana kwe-microenvironment yamaselula, lawula ukubonakaliswa kwamaselula kanye ne-metabolism.94 Izimpawu kanye nezinguquko eziguquguqukayo zama-athomu e-exosome wempahla abonisa ngokuqondile izici kanye nezinguquko eziguquguqukayo zamangqamuzana esimila sabazali, 95 futhi okuyisisekelo sokusebenzisa ama-exosomes ekuxilongeni nasekubikezelweni komdlavuza, kanye nokubikezela impendulo yomuntu ngamunye ekwelashweni kwe-anticancer. ..96
Izindlela zaselabhorethri zendabuko zokuhlukanisa nokuhlaziya ama-exosomes ziyinkimbinkimbi, izinyathelo eziningi, futhi zidla isikhathi, kufaka phakathi i-ultracentrifugation, filtration, i-chromatography yokukhishwa kwesayizi, ukuhlanzwa kwe-immunoaffinity, ukuchithwa kwe-Western, i-enzyme-linked immunosorbent assay (ELISA), i-PCR, nokuhlaziywa kokugeleza.amasistimu amancane namapulatifomu e-lab-on-a-chip asebenzisa i-micro/nanotechnology athuthukiswa kabanzi ukuze kutholakale ama-exosomes asheshayo, afaneleka endaweni.Ukuhlaziywa kokulandelela i-Nanoparticle (NTA) kuyindlela esetshenziswa kakhulu yokubonisa usayizi nokugxila kwama-exosomes, okuhlanganisa izindlela ezifana ne-magnetic nanoparticles nama-polyhydroxyalkanoates.Izindlela ze-Microfluidic kanye ne-electrochemical nazo zingathola ngokushesha ama-exosomes ezivunweni eziphezulu.
Amaprotheni e-Exosomal ayizimpawu ezibalulekile zokuxilongwa kwe-HCC.Ocwaningweni lwe-Arbelaiz, izinga le-98 RasGAP SH3 binding protein (G3BP) kanye ne-polymeric immunoglobulin receptor (PIGR) laliphakanyiswe kakhulu kuma-exosomes asuselwa ku-HCC, futhi ukusebenza kahle okuhlanganisiwe okuhlanganisiwe kwamaphrotheni amabili kwakungaphezu kwalokho kwe-AFP.Ukugcwala kwe-ayoni kuyisici esibalulekile esinomthelela ekuthuthukisweni kwe-HCC.U-Tseng ubike ukuthi i-hepcidin ingase idlale indima ebalulekile ekumelaneni ne-HCC.Ama-Exosomes angu-99 athathwe ku-sera yeziguli ze-HCC ayenenombolo yekhophi ephakeme kakhulu yezinhlobonhlobo ze-hepcidin mRNA kunozakwabo abanempilo, okuphakamisa ukuthi i-hepcidin ingase ibe i-biomarker yokuxilonga inoveli ye-HCC.I-protein ye-14-3-3ζ kuma-exosomes akhiqizwa yi-100 HCC inganciphisa ukusebenza kwe-T cell, ukwanda, nokuhlukaniswa futhi ingafaka ukuguqulwa kwe-T cell ibe amaseli T alawulayo, okuholela ekuncipheni kwe-T cell.101 Lokhu kusekelwa izifundo eziningana eziphenya ukugwenywa kwesimila ekugadweni kwamasosha omzimba, 102 okungase kube nomthelela ku-HCC tumorigenesis.
Ngokungeziwe ebukhoneni be-ecRNA ku-plasma noma ku-serum, ama-exosomes anothiswe yi-RNA angasetshenziselwa isiteji sesikhathi sangempela esingahlaseli ekuhlolweni kwangaphambi kwesikhathi kwesimila kanye nokunquma ukuvela kwesimila kanye nokusabela ekwelashweni.Izinga le-exosomal miRNA-21 ku-serum yegazi eqenjini le-HCC laliphindwe izikhathi ezingu-2.21 kuneqembu le-CHB, futhi eqenjini le-HCC laliphindwe izikhathi ezingu-5.57 kunabantu abanempilo.Ocwaningweni luka-Wang, ama-exosomes akhuphule kakhulu i-HCC uma kuqhathaniswa neziguli ezine-cirrhotic ezinamavelu e-AUC angu-0.83 (95% CI 0.74–0.93) kanye no-0.94 (95% CI 0.88–1.00).104 Idatha etholiwe yacacisa ukubandakanyeka kwama-molecule e-exosomal cargo ethile ekulawuleni i-oncogenesis nokuqhubeka kwe-HCC.105 Ukubonakaliswa kweSerum ye-miR-221, miR-103, miR-181c, miR-181a, miR-93 kanye ne-miR-26a kuyahambisana.kanye ne-metastasis, kanye namazinga e-miR21 ayephezulu kakhulu ezigulini ze-HCC kunezilawuli ezinempilo futhi nasezigulini ze-CHB. I-102 LncRNA yayinevelu yokuxilonga engaba khona ku-HCC.Ucwaningo luye lwabonisa ukuthi ama-exosomes atholakala ku-sera yeziguli ze-HCC anamazinga aphezulu kakhulu e-LINC00161, i-LINC000635, ne-lncRNA ecushwe ngokuguqula isici sokukhula-β kuneziguli ezingenayo i-HCC, futhi lawa ma-lncRNA ahlotshaniswa kakhulu nesiteji se-TNM kanye nevolumu yesimila.110 Conigliaro et al.Ama-CD90+ exosomes atholakale eveza amazinga aphezulu e-lncRNAH19, okukhulise kakhulu ukukhululwa kwe-vascular endothelial growth factor (VEGF) kanye nokukhiqizwa kwe-VEGF-R1 receptor, ngaleyo ndlela kukhuthaze i-angiogenesis.I-93 CircRNAs ingolunye uhlobo lwe-exosomal ncRNAs - evezwa emazingeni aphansi kodwa azinzile kuzo zonke izinhlobo zezilwane, ama-circRNA aphinde abonise ukucaciswa kohlobo lweseli, uhlobo lwethishu, isigaba sokuthuthuka, nomsebenzi wokulawula.Ama-circRNA angu-111 angama-biomarker okuxilonga omdlavuza wangaphambi kwesikhathi kanye nongena kancane kancane.112 Ukuhlolwa komtholampilo kwakamuva kubonise ukuthi ukucaciswa kwe-miRNA ngayinye ekubikezeleni i-HCC akulungile.Ngakho-ke, ukutholwa okuyinkimbinkimbi kusetshenziswa izivivinyo eziningi (isb, i-miR-122 ne-miR-48a kuhlanganiswe ne-AFP) kungase kuthuthukise ukuhlonzwa kwe-HCC yasekuqaleni kanye nokuhlukaniswa kwe-HCC kusukela ku-cirrhosis.100
Iziguli ezine-CHB kanye ne-cirrhosis yesibindi ziyiqembu elivame kakhulu elisengozini enkulu yokuthuthukisa i-HCC.Emaqenjini asengozini enkulu, uma impendulo eqhubekayo ye-virological isifinyelelwe, isu lokugada elingabizi kakhulu elisekelwe engcupheni ye-HCC kufanele lenziwe, futhi ukuhlolwa kusenesikhathi kuyisihluthulelo sokuthuthukisa ukuxilonga nokwelashwa kwe-HCC ngenani eliphezulu lokusebenza ngempumelelo kwe-2. ..Izindlela zokuhlolelwa umdlavuza kusenesikhathi zinemikhawulo eminingi: izindlela zokuhlola kusenesikhathi azikathuthukiswa ezinhlotsheni eziningi zomdlavuza, futhi ukubambelela ngokuqinile kwemithi njalo njalo kuncane.Uma kuqhathaniswa nezindlela zokuhlola zakuqala zendabuko, ubuchwepheshe be-liquid biopsy bunezinzuzo ezisobala: ukutholakala kalula kwesampula, ukutholwa kwe-panrac, ukuzala kabusha kwesampula okuhle, kanye nokuphendula okusebenzayo ku-tumor heterogeneity.Uma kubhekwa ukusebenza kahle kwezindleko zezindlela ezihlotshaniswa ne-liquid biopsy, ukusetshenziswa kwazo ekuhlolweni kwe-HCC akuzange kuhlolwe njalo.Naphezu kwentuthuko ekutholeni okunembile ezingeni lamangqamuzana, i-fluid biopsy ibiza kakhulu ukuthola i-HCC ezigulini eziqondiwe, ikhawulela ukusetshenziswa kwayo okusabalele uma kuqhathaniswa nezinqubo ezithile zokucabanga ezifana ne-ultrasound kanye ne-magnetic resonance imaging.113,114 Nokho, ucwaningo lwangaphambilini lubonise ukuthi i-biopsy ye-liquid ibonise inzuzo enkulu ngokweminyaka yokuphila ehlelwe yikhwalithi (QALYs).115 Izinzuzo ze-liquid biopsy ku-carcinoma yokuqala yesisu kanye ne-nasopharynx nazo zibonisiwe.116,117 Umbono wamanje wukuthi i-liquid biopsy ingahambisana nezimpawu ze-serum biomarker kanye nokuhlolwa kwe-radiological ekutholweni nasekuxilongweni kwamathumba.117 118
Ngokusho kwezincwadi zamanje, ubuchwepheshe be-fluid biopsy buye babonisa ukuzwela okuphezulu kakhulu nokucacile ekuhlolweni kokuqala kwamaqembu asengozini enkulu yomdlavuza wesibindi.Kungakhathalekile ukuthi hlobo luni lwe-fluid biopsy, ingakwazi ukuhlukanisa i-HCC kubantu abasengozini enkulu ngaphandle kwe-HCC, iphakamisa ukubaluleka kokuhlolwa kusenesikhathi njengoba kubonakala umehluko phakathi kwabantu abasengozini enkulu kanye nabanempilo.I-ctDNA inohhafu wempilo emfushane futhi ingasetshenziswa ukuthola i-HCC, ngakho-ke noma yiziphi izinguquko ku-cDNA etholakala ngesimila zinganikeza ubufakazi obuphathekayo besikhathi sangempela bokuqhubeka kwesimila, ikakhulukazi ezimila ezincane.Izinga eliphezulu le-ctDNA likhombisa ukukhula nokusabalala komdlavuza futhi liyinkomba yokuqala yokuqhubeka nokuphindeka.Ngaphezu kwalokho, ngokusekelwe emiphumeleni ye-ctDNA, iziguli zingathola ukwelashwa komuntu ngamunye kanye nokulandelela.119 Amasayithi athile e-methylation angase abe umaka ongcono kune-AFP wokuhlonzwa kusenesikhathi kwe-HCC namaqhuqhuva okucijile.Ezimweni ezihlehliswa kabusha ze-HCC, amazinga aphezulu e-cDNA ayizinkomba zokuhlasela kwe-microvascular kanye nokuphindaphinda kwangemva kokuhlinzwa kanye ne-metastasis.Izinguquko enambeni yekhophi zihlotshaniswa nokusinda kweziguli ezine-HCC.Kungacatshangwa ukuthi ukuhlolwa kwe-cDNA kungase kuhileleke ekwelashweni kukonke kwe-HCC, futhi i-cDNA ingasebenza njengenkomba ephumelelayo yokuguquguquka kokwelapha.Omaka abasuselwe ekuguquleni okuthile kofuzo ku-ctDNA bamukelwe yiziqondiso zomtholampilo ukuze kubikezelwe ukusebenza kahle nokuqapha ukumelana nomuthi.Ukuhlolwa kwe-ctDNA kungase kube ithuluzi elisebenziseka kakhulu le-biopsy eliwuketshezi lokuhlola kusenesikhathi.Ama-CTC nawo adlala indima ebalulekile ekuhlolweni kusenesikhathi kwamaqembu e-HCC asengozini enkulu.Omaka abahlukahlukene bama-CTC ahlotshaniswa ne-HCC babaluleke ngokukhethekile ekuqaleni, ekuthuthukisweni, nasekuphindeni kwe-HCC.Njengama-membrane vesicles, ama-exosome abandakanyeka ekuxhumaneni kwe-intercellular, ikakhulukazi kumaseli e-HCC.Ama-microRNA ajikelezayo azinzile egazini futhi ngaleyo ndlela angase abe usizo kakhulu ekuhlolweni kwangaphambi kwesikhathi kwe-HCC.Kancane kancane, amaprotheni e-exosomal kanye nama-exosome acebile nge-RNA atholakala, futhi ukusebenza kwawo kokubikezela kwe-HCC kwaqinisekiswa.Kuyathakazelisa ukuthi i-etiologies ehlukene ye-HCC ingase futhi ihlotshaniswe noshintsho oluhlukile, ngakho-ke singakhetha ama-biomarker ahlukene ukuze sihlolwe kusenesikhathi ngokususelwe ku-etiologies ehlukene ye-HCC.120
Kodwa-ke, amasu amanje we-fluid biopsy ayangabazeka mayelana nokuzinza futhi awakwazi ngokuzimela ukwenza ukuhlolwa kwangaphambi kwesikhathi noma ukuqapha i-HCC, kodwa asengahambisana nokuhlolwa komuntu ngamunye kanye nokuxilongwa.121 Njengohlobo lwe-biopsy ewuketshezi, ukutholwa nokuthwebula izithombe kwe-ctDNA, i-CTC, i-cfRNA ne-AFP ehlotshaniswa ne-exosome noma i-PIVKA-II kunezinhlelo zokusebenza ezithembisayo ekuxilongweni kokuqala nasekuxilongweni kwe-HCC.Kodwa-ke, indlela eqondile yokukhishwa kwe-ctDNA egazini kusazocaciswa.Ukwembula izici eziyisisekelo zebhayoloji ze-ctDNA kungase kusize ukusetshenziswa kwayo njengomaka.Inani elincane le-ctDNA ekusatshalalisweni kanye nezidingo zokuphatha isampula eziqinile ziyizinselele zokuqaliswa komtholampilo kokutholwa kwe-cDNA ku-HCC.Ngaphezu kwalokho, ukuguqulwa kofuzo akunazo izici ezithile ezivumela ukuhlonza okunembile kwezakhi zomdlavuza.Njengoba ukuhlukahluka okuningi kofuzo kanye ne-somatic kukhona futhi ezicutshini ezivamile, ukuguqulwa kofuzo okuhlonzwe i-fluid biopsy kungase kube usizo olulinganiselwe ekuhloleni kwangaphambi kwesikhathi kwe-HCC.122 Imikhawulo yezakhi zofuzo eziqondisiwe ezichazwe kahle kanye nama-biomarker asiza ukuhlukanisa i-cDNA ne-non-tumor DNA yizindaba ezibaluleke kakhulu ekusetshenzisweni kwe-cDNA.ukuntuleka kokusebenziseka kwezimpawu ezibucayi neziqondile zokutholwa kwama-CTC.Amaseli asebenzayo kuphela anamandla e-metastatic atholakele, futhi inhlanganisela efanele yomaka abathuthukisiwe be-CSC ibingacacile.Ukuhlukaniswa kwama-CTCs kusikompilo nokuhlolwa kwamaphrofayili awo aguqukayo nakho kuwumsebenzi oyinselele.Ngenxa yezinkinga zokuhlonza, ukuhlukaniswa kanye nokuhlanzwa kwama-exosomes, indlela ethile ye-molecular ayikacaci, futhi izifundo zangaphambilini mayelana nendlela ye-exosomes ne-HCC bezingakajuli, kanye nendlela ama-miRNAs, i-lncRNAs, namaprotheni ahlelwa abe ama-exosomes. , futhi akucaci ukuthi ukuthatha i-exosome kuyinqubo yohlobo oluthile.Ukusetshenziswa kwama-exosomes ekuxilongeni nasekulapheni i-HCC kusesesigabeni sangaphambi komtholampilo.Ukuntuleka kokumiswa kwezinqubo ze-liquid biopsy, njengohlobo lwamashubhu asetshenziselwa ukuqoqa igazi, umthamo wegazi, ukugcinwa kwesampula nokutholwa, ukuhlukaniswa nokunothisa, kungase kuvimbele ukusetshenziswa kwazo emisebenzini evamile yomtholampilo ngenxa yomehluko wezinqubo kuzo zonke izikhungo zezokwelapha.Ukusebenza kwe-liquid biopsy ekuhlolweni kwangaphambi kwesikhathi, ukuxilongwa, ukulinganisa ukusebenza kahle, nokubikezelwa kwe-HCC kusazocutshungulwa, ikakhulukazi emaqenjini asengozini enkulu.Ubuchwepheshe be-Liquid biopsy bunamandla amakhulu futhi kulindeleke ukuthi busetshenziswe kabanzi emtholampilo womdlavuza wesibindi maduze nje.
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