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Ding Jingnuo, Zhao Weifeng, Lefapha la Mafu a tšoaetsanoang, Sepetlele sa Pele se Kopanetsoeng sa Univesithi ea Suzhou, Motse oa Suzhou, Profinseng ea Jiangsu, 215000 Tel.Lihlahala tsa tsamaiso ea tšilo ea lijo tse nang le lilemo tse 5 tsa ho phela ha 14.1%.Bakuli ba bangata ba nang le HCC ba fumanoa ba le boemong bo tsoetseng pele, kahoo tlhahlobo ea pele e hlokahala ho fokotsa ho shoa ha HCC.Ntle le matšoao a tloaelehileng a ho lemoha a kang serum alpha-fetoprotein (AFP), lens lectin-reactive alpha-fetoprotein (AFP-L3), le prothrombin e sa tloaelehang (prothrombin e bakoang ke ho haelloa ke vithamine II, PIVKA-II), mekhoa ea mokelikeli oa biopsy. E bonts'itsoe e le ea bohlokoa ho hlahlojoa ha HCC.Ha ho bapisoa le lits'ebetso tse hlaselang, biopsy ea mokelikeli e khona ho bona li-metabolite tse kotsi tse potolohang.Mekhoa ea Fluid biopsy e lemoha lisele tsa hlahala tse potolohang, DNA ea tumor e potolohang, RNA e potolohang, le li-exosomes 'me li sebelisoa bakeng sa tlhahlobo ea pele, tlhahlobo le tlhahlobo ea pele ea HCC.Sengoliloeng sena se lekola baeloji ea limolek'hule le ts'ebeliso ea mekhoa e fapaneng ea mokelikeli oa biopsy ho khetholla li-biomarker tse tšepisang tseo e ka bang likhetho tse sebetsang bakeng sa tlhahlobo ea pele ea HCC ho ntlafatsa tlhahlobo ea pele ea lihlopha tsa HCC tse kotsing e kholo.Mantsoe a bohlokoa: mokhoa oa mokelikeli oa biopsy, hepatocellular carcinoma, sehlopha se kotsi haholo.
Hepatocellular carcinoma (HCC) ke hlahala e kotsi e tloaelehileng ea tšilo ea lijo, e boemong ba botšelela har'a linyeoe tse ncha tsa lihlahala tse kotsi ho banna le basali.Lefatšeng ka bophara, mofets'e oa sebete ke sesosa sa boraro se bakang lefu la mofets'e kamora mofets'e oa matšoafo le oa colorectal, e leng karolo ea 8.3% ea mafu a amanang le mofets'e ho tsoa ho li-neoplasms tsohle tse mpe.1 Polelo ea HCC e amana haufi-ufi le boemo ba ho hlahlojoa.Mabaka a ka sehloohong a ho phela hampe ho HCC ke metastase ea intrahepatic, portal venous tumor thrombi, le metastase e hole e thibelang ho khutlisoa, 'me tse ngata tsa litšobotsi tsena li se li le teng ho bakuli nakong ea tlhahlobo.
Ho ipapisitsoe le litataiso tsa tlhahlobo le kalafo, mabaka a ka sehloohong a kotsi bakeng sa ho hlahisa HCC ke ho thatafala ha sebete, kokoana-hloko e sa foleng ea hepatitis B (HBV) kapa hepatitis C (HCV), lefu la sebete sa mafura a joala, le lefu la sebete le se nang joala (NAFLD). ).2 Ho phaella moo, mabaka a kotsi bakeng sa HCC a akarelletsa ho ja lijo tse nang le chefo e nang le aflatoxin, schistosomiasis, lisosa tse ling tsa lefu la ho thatafala ha sebete, histori ea lelapa ea kankere ea sebete, lefu la tsoekere, botenya, ho tsuba le kotsi ea sebete e bakoang ke lithethefatsi.Lihlopha tse kotsing e kholo ea lilemo tse 35 le 45 li lokela ho hlahlojoa khafetsa ke lingaka.Tlhahlobo ea pele ke leano la bohlokoa la kalafo ea pele ho ntlafatsa bophelo bohle ba bakuli ba HCC.
Li-biomarker tse kang AFP, AFP-L3 le PIVKA-II li khothaletsoa bakeng sa tlhahlobo ea pele ea HCC3,4.Mekhoa ea biopsy ea metsi e bonts'itse litholoana tse ts'episang tlhahlobong ea pele le tlhahlobo ea kalafo.5,6 Khatelo-pele e kholo e entsoe ka biopsy ea mokelikeli oa HCC, e ka 'nang ea e-ba le kutloisiso e phahameng le e khethehileng ho feta matšoao a serum a sebelisoang ka tloaelo a kang AFP (Letlapa la 1).
AFP ke biomarker e sebelisoang haholo ho HCC 'me hajoale ke eona biomarker e nang le lintlha tse ngata e sebelisoang haholo bakeng sa tlhahlobo ea pele, tlhahlobo le tlhahlobo ea lefu lena.Boemo bo sa khaotseng ba AFP bo nkoa e le sesosa sa kotsi bakeng sa tsoelo-pele ea HCC.7,8 Tekanyo ea ho lemoha ha hepatocellular carcinoma (sHCC) e ntse e eketseha ka tsoelo-pele ea ultrasound le computed tomography, 'me AFP e fumanoe e le e sa tsotelleng ka ho khetheha ho lemoha hHCC ts'ebetsong ea meriana.Ho ea ka phuputso ea retrospective multicentre9, AFP positive e fumanoe ho 46% (616/1338) ea linyeoe tsa HCC le 23.4% (150/641) ea linyeoe tsa sHCC.Ho feta moo, maemo a AFP a phahame ho bakuli ba nang le lefu la sebete le sa foleng le ho thatafala ha sebete.10 Kahoo, AFP e na le phello e fokolang ea ho hlahloba sHCC.11 Ho ea ka Asia-Pacific Clinical Practice Guidelines for Hepatocellular Carcinoma, tšebeliso ea AFP ha e khothalletsoe.12 Bopaki ba lingaka bo bontša hore PIVKA-II e phahametse AFP ha ho phekoloa HCC le hore motsoako oa PIVKA-II le AFP o na le boleng bo phahameng ba tlhahlobo ho HCC.13 Ha ho bapisoa le biopsy ea lithane, biopsy ea mokelikeli e fumana haholo-holo metabolite e amanang le hlahala marong a 'mele (mali, mathe, pleural fluid, cerebrospinal fluid, kapa moroto) 'me ha e hlaseloe haholo liseleng.14 Ntle le moo, li-biopsies tsa mokelikeli li ka bonts'a likarolo tse mpe tse sieo liseleng tsa mantlha tsa hlahala.15 Li-biopsies tsa metsi ha li e-so hlahlojoe ts'ebetsong ea bongaka bakeng sa mefuta eohle ea lihlahala, empa bokhoni ba tsona ba ho hlahloba mofetše bo hohela tlhokomelo ea lingaka.16 Fluid biopsy e ka lemoha lisele tsa hlahala tse potolohang (CTCs), DNA ea hlahala e potolohang (cDNA), e potolohang RNA (ecRNA) e sa lefelloeng, le li-exosomes.Sengoliloeng sena, re tla tšohla litšobotsi, karolo, le ts'ebeliso ea mekhoa e fapaneng ea biopsy ea mokelikeli tlhahlobong ea pele ea lihlopha tsa HCC tse kotsing e kholo.
DNA ea Extracellular (cfDNA) ka lisampole tsa mali ho batho ba phetseng hantle e qalile ho hlalosoa ka 1948 ke Mandel et al.17 cfDNA ke sekhechana sa DNA se se nang lisele se ka bang bolelele ba 160–180 bp, se tsoang haholo-holo ho li-lymphocyte le lisele tsa myeloid.ctDNA ke karolo e itseng ea DNA e fetotsoeng e lokollotsoeng ke lisele tsa hlahala maling a peripheral, e emelang tlhaiso-leseling ea genomic ea lisele tsa tumor kamora lits'ebetso tse itseng tsa pathophysiological, ho kenyelletsa necrosis, apoptosis, le excretion.Karolo ea ctDNA ka kakaretso ea cfDNA e fapana haholo ho ea ka mofuta oa hlahala, 'me likaroloana tsa cDNA li tlalehoa li le ka tlase ho 167 bp ka bolelele.18 Boithuto ba Underhill bo bontšitse hore likhechana tsa cfDNA hangata li khuts'oane ho feta cfDNA e tloaelehileng.19 Ha ho bapisoa le batho ba phetseng hantle, bolelele bohle ba likaroloana tsa cfDNA maling a bakuli ba mofets'e bo bokhuts'oane, kahoo cfDNA e ka sebelisoa e le sesupo sa tlhahlobo ea pele ea hlahala.Ntlafatso ea li-subsets tse ling tsa bolelele ba sekhechana sa cfDNA e ka ntlafatsa ho fumanoa ha cDNA e amanang le lihlahala tse tiileng tse se nang metastatic.Liphuputso li bontšitse hore ctDNA e fumanoa ho feta 75% ea kankere e tsoetseng pele ea pancreatic, colon, senya, mala, sebete, mahe a bomme, matsoele, melanoma, le mofetše oa hlooho le molala.20,21 Leha ho le joalo, palo ea ctDNA maling e itšetlehile ka sebaka sa hlahala.22 Phuputsong e entsoeng ke Bettegoud, bakuli ba nang le kankere ea mala, ea matsoele, ea sebete, ea matšoafo le ea tšoelesa ea senya, ba ile ba fumanoa ba e-na le litekanyetso tse phahameng tsa cDNA maling a bona ho feta mefuta e meng ea mofetše.Ka lehlakoreng le leng, ho bakuli ba nang le mofetše oa molomo, mofetše oa pancreatic, mofetše oa mala le glioma, khatello ea cDNA maling e ne e le tlase.mashome a mabeli a motso o le mong
Hobane ctDNA e na le liphatsa tsa lefutso tse tšoanang le lisele tsa mantlha tsa hlahala, cDNA e ka sebelisoa ho bona liphetoho tse fapaneng tsa tumor le liphetoho tsa epigenetic, ho kenyelletsa methylation, hydroxymethylation, phapang e le 'ngoe ea nucleotide, le ho fapana ha linomoro.mashome a mabeli a metso e meraro
DNA methylation ke e 'ngoe ea liphetoho tse atileng haholo tsa epigenetic tse bakang khatello ea liphatsa tsa lefutso.Ha ho bapisoa le lisele tse tloaelehileng, ho na le liphapang ka kakaretso ea methylation ea tumor cell genome, haholo-holo ho methylation ea liphatsa tsa lefutso tsa tumor suppressor, tse ka fumanoang qalong, ho fana ka maikutlo a hore liphetoho tsa DNA methylation e ka 'na ea e-ba pontšo ea pele ho nako. ho fumanoa ha tumorigenesis.Liphatsa tsa lefutso tsa "tumor suppressor" tse amanang le HCC li ka emisoa ke methylation e khothalletsang, kahoo e susumetsa tumorigenesis.24 DNA methylation ke lets'oao le loketseng bakeng sa tlhahlobo ea pele ea lihlahala ka lebaka la boits'oaro ba eona ba lisele, ho bonoa, le boikemelo ba lilemo.Ho phaella moo, DNA methylation e tloaelehile haholo ha e bapisoa le liphetoho tsa somatic hobane ho na le libaka tse ngata tse lebisitsoeng le libaka tse ngata tse fetotsoeng tsa CpG sebakeng se seng le se seng sa genome e lebisitsoeng.25 Ho phaella libakeng tse ngata tsa CpG, palo e kholo ea loci e ikemetseng ea hypermethylated ho ctDNA e khethiloe ho DBX2, THY1, MT1M, INK4A, VIM, FBLN1, le RGS10.26 Xu et al.Papiso ea lisampole tsa cfDNA ho tsoa ho bakuli ba 1098 HCC le litsamaiso tse 835 tse phetseng hantle e ne e le liphatsa tsa lefutso tse amanang le HCC li fumanoe li amana ka matla le li-signature tse tsamaellanang tsa plasma cDNA methylation.25 Ho ipapisitsoe le tlhahlobo ea laboratori, ho ile ha etsoa mohlala o boletsoeng esale pele o nang le matšoao a 10 a methylation a nang le kutloelo-bohloko le tse ikhethang tsa 85.7% le 94.3%, ka ho latellana, 'me matšoao ana a ne a amana haholo le boima ba hlahala, sethala sa hlahala, le karabelo kalafong.Liphetho tsena li bonts'a hore ts'ebeliso ea matšoao a cDNA methylation e na le ts'episo e kholo ho hlahlojoeng, ho lekola, le ho prognoza ha HCC.Moetsong oa methylation o nang le liphatsa tsa lefutso tse tharo tsa aberrantly methylated (APC, COX2, RASSF1A) le miRNA e le 'ngoe (miR203) e hlahisitsoeng ke Lu et al27, kutlo le boits'oaro ba mohlala oa 27 bakeng sa ho fumana HCC e amanang le HBV li ne li bapisoa.80%.Ho phaella moo, mohlala o ka lemoha 75% ea bakuli ba HCC ba sa tsejoeng ba nang le boemo ba AFP ba 20 ng / mL.Lefutso bakeng sa lelapa la Ras-associated domain 1A protheine (RASSF1A) ke eona e ka sehloohong e pheta-phetoang tatellano ea DNA ho genome ea motho.Araujo et al.e fihletse qeto ea hore hypermethylation ea mothetsi oa RASSF1A e ka ba biomarker ea bohlokoa bakeng sa tlhahlobo ea pele ea HCC le sepheo sa molek'hule se ka bang teng bakeng sa phekolo ea epigenetic.28 Phuputsong e 'ngoe, serum RASSF1A promoter hypermethylation e fumanoe ho 73.3% ea bakuli ba HCC.29 Nako e telele ea nucleotide element 1 (LINE-1) ke mokena-lipakeng o mong ea sebetsang haholo oa retrotransposition.Hypomethylation ea LINE-1 e fumanoe ho DNA ea 66.7% ea lisampole tsa serum ea HCC 'me e ne e amahanngoa le ho khutlela pele le ho phela hampe ka mor'a ho tsosolosoa ka matla.29 Hypermethylation ke mokhoa o tloaelehileng oa liphatsa tsa lefutso o phethang karolo e ikhethang ho nts'etsopele ea sebete sa sebete le HCC.30 Ka lehlakoreng le leng, hydroxymethylation ke ts'ebetso ea demethylation e etsang hore liphatsa tsa lefutso li tsosolosoe le ho hlahisa maikutlo, 'me ho lemoha sehlahisoa sa 5-hydroxymethylcytosine (5-hmC) ts'ebetsong ena ho ka sebelisoa ho khetholla hlahala.Methylation le hydroxymethylation ea cDNA li amahanngoa le tumorigenesis 'me li ka kenya letsoho ho hlahloba HCC pele ho nako.Phuputsong ea lithuto tse 2554, li-5-hmC tse 31 tsa genome-wide 5-hmC li fumanoe ka lisampole tsa cfDNA, 'me liphatsa tsa lefutso tse 32 li ile tsa khetholloa ka ho bapisa tatellano ea 5-hmC ho bakuli ba HCC le lihlopha tse kotsing e kholo tse kang ba nang le mafu a sa foleng.Mekhoa ea ho hlahloba mafu a sebete.le lefu la sebete.Mohlala ona o ne o phahametse AFP ka ho khetholla HCC ho lisele tse se nang hlahala.
Liphetoho tse hlahang libakeng tsa likhoutu li ka lebisa mefuteng e sa tloaelehang ea mongolo, e ka lebisang liphetohong tsa tatellano ea liprotheine mme qetellong mofetše.Mefuta e le 'ngoe ea li-nucleotide ke matšoao a bohlokoa a genomic bakeng sa tlhahlobo ea tumor ea pele ka lebaka la ts'epo ea bona e phahameng ea lisele le boits'oaro bo phahameng ba hlahala le lisele.Lithuto tse ngata tse amanang le HCC tse sebelisang tatellano ea moloko o latelang (NGS) bakeng sa exome le tatellano ea lefutso ea mofetše li bonts'itse liphatsa tsa lefutso tse tloaelehileng tse kang TP53 le CTNNB1, hammoho le tse 'maloa ho kenyelletsa ARID1A, MLL, IRF2.Liphatsa tsa lefutso tse ncha, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3 le JAK1 li bontša maemo a itekanetseng a phetoho. Tlhahlobo ea ts'ebetso ea liphatsa tsa lefutso tse feto-fetohang e fana ka maikutlo a hore liphetoho tsa ho fetola chromatin, Wnt/β-catenin le JAK/STAT signal transduction, P53-cell cycle pathway, epigenetic modifiers, oxidative stress pathways, PI3K/AKT/MTOR tsela le RAS/RAF/ MAPK kinase pathway e phetha karolo ea bohlokoa ho HCC oncogenesis.32,33 Phuputsong eo ho eona liphetoho tse amanang le tumor li fumanoeng, Huang et al o fumane hore makhetlo a mangata a liphetoho tse amanang le tumor tse itšetlehileng ka ctDNA e ne e le 19.5%, 'me e khethehileng e ne e le 90%. .34 Ho phaella moo, bakuli ba neng ba e-na le tlhaselo ea methapo ea mali ba ne ba ka 'na ba e-ba le liphetoho tsa ctDNA (P = 0.041) le ho phela ha nako e khutšoanyane ho se nang ho khutla (P <0.001). Tlhahlobo ea ts'ebetso ea liphatsa tsa lefutso tse feto-fetohang e fana ka maikutlo a hore liphetoho tsa ho fetola chromatin, Wnt/β-catenin le JAK/STAT signal transduction, P53-cell cycle pathway, epigenetic modifiers, oxidative stress pathways, PI3K/AKT/MTOR tsela le RAS/RAF/ MAPK kinase pathway e phetha karolo ea bohlokoa ho HCC oncogenesis.32,33 Phuputsong eo ho eona liphetoho tse amanang le tumor li fumanoeng, Huang et al o fumane hore makhetlo a mangata a liphetoho tse amanang le tumor tse itšetlehileng ka ctDNA e ne e le 19.5%, 'me e khethehileng e ne e le 90%. .34 Ho phaella moo, bakuli ba neng ba e-na le tlhaselo ea methapo ea mali ba ne ba ka 'na ba e-ba le liphetoho tsa ctDNA (P = 0.041) le ho phela ha nako e khutšoanyane ho se nang ho khutla (P <0.001).Ts'ebetso ea phetoho ea liphatsa tsa lefutso e fana ka maikutlo a hore liphetoho ho lokisoeng ha chromatin, pontšo ea Wnt/β-catenin le JAK/STAT, P53 cell cycle pathway, epigenetic modifiers, oxidative stress pathway, PI3K/AKT/MTOR pathway, le RAS/RAF/ MAPK kinase pathway plays karolo ea bohlokoa ho HCC tumorigenesis.32,33 Phuputsong e ileng ea fumana liphetoho tse amanang le hlahala, Huang et al.e fumane hore khafetsa ea liphetoho tse amanang le hlahala e itšetlehileng ka ctDNA e ne e le 19.5% mme e ikhethang e ne e le 90%..34 Кроме того, у пациентов сосудистой инвазией чаще мстречались мутации цДНК (P=0,041) le более короткая безрецивыдиживя <P=0,041. .34 Ho phaella moo, bakuli ba nang le tlhaselo ea methapo ba ne ba e-na le liphetoho tse ngata tsa cDNA (P = 0.041) le ho phela ha nako e khutšoanyane ho se nang maloetse (P <0.001).Tlhahlobo ea ts'ebetso ea liphatsa tsa lefutso tse fetotsoeng e senoletse phetoho ea chromatin, pontšo ea Wnt/β-catenin le JAK/STAT, tsela ea potoloho ea lisele tsa P53, li-epigenetic modifiers, tsela ea khatello ea oxidative, tsela ea PI3K/AKT/MTOR, le RAS/RAF/MAPK kinase pathway e bapala karolo ea bohlokoa ho oncogenesis ea HCC. 32 33 在 一发现 的检测 的 中 中 的 的 的 的 的 的 的 的 的 the 19.5%, 特异性 为 为 的 血管 血管 血管 血管 血管 血管 血管 血管 血管 血管 血管 血管 血管 有 可能 可能 可能突变（P=0.041）和更短的无复发生存期（P<0.001). 32.33 在在短的无复发生存期（P<0.001)32,33 Phuputsong e fumaneng liphetoho tse amanang le tumor, Huang et al.o fumane hore liphetoho tse amanang le hlahala li ne li itšetlehile ka 19.5% ho cDNA e khethehileng ea 90% 34. Ho phaella moo, bakuli ba neng ba e-na le tlhaselo ea methapo ba ne ba e-na le monyetla oa ho hlahisa cDNA.мутация (P = 0,041) le более короткая безрецидивная выживаемость (P <0,001). phetoho ea phetoho (P=0.041) le ho phela nako e khutšoanyane ho se nang maloetse (P<0.001).Mofuta o mong o tloaelehileng oa mokhanni oa HCC ke TP53, e nang le sekhahla sa phetoho e fetang 30%.Liphuputso li bonts'itse hore khafetsa TP53 ea liphetoho ho ctDNA maling le morotong e tloha ho 5% ho isa ho 60%.35 Boithuto ba Johan bo bonts'itse hore ctDNA mutation spectrum qetellong ea HCC e na le sekhahla se ts'oanang sa phetoho ho HCC ea pele, ho kenyeletsoa mothetsi oa TERT (51%), TP53 (32%), CTNNB1 (17%), PTEN (8%), liphetoho ho AXIN1 ., ARID2, KMT2D le TSC2 (6% ka 'ngoe).36 Oncogene ea β-catenin (CTNNB1) e phetha karolo ea bohlokoa tseleng ea pontšo ea Wnt.The transcription coactivator CTNNB1 e ka khothaletsa tlhahiso ea liphatsa tsa lefutso, e leng se ka lebisang ho ata ha lisele, ho thibela apoptosis, le angiogenesis.CTNNB1 e ka boela ea sebelisana le TERT ho susumetsa phetoho ea hepatocyte.33 Motlatsi oa TERT hangata o fetoloa lihlahala tse ling tse tiileng.Liphetoho ho TERT, e 'ngoe ea liphetoho tsa pele tsa liphatsa tsa lefutso phetohong e mpe ea HCC, e ka lebisa ho ts'ebetsong ea telomerase ho cirrhotic hepatocyte' me e ka khothalletsa ho ata le ho thibela botsofali.Liphetoho ho mothetsi oa 33-37 TERT li tlalehiloe hore li etsahetse ho 59-90% ea bakuli ba nang le li-nodule tsa sebete tse ngata le HCC ea pele 'me ba amahanngoa le ho pholoha.38
Liphetoho tsa nomoro ea kopi (CNA) ke mofuta oa bohlokoa oa liphetoho tsa somatic.Lipatlisiso li bonts'itse hore moroalo o atileng le o tsepamisitsoeng oa CNA ke lets'oao la genomic le khonang ho bolela esale pele ho kenella ha 'mele oa ho itšireletsa mafung le ho qheleloa ka thoko mefuteng e meng ea mofetše.39 Pontšo ea ho kenella ka mafolofolo, ts'ebetso e phahameng ea cytolytic, ho ruruha ho matla le matšoao a lefutso a amanang le tlhahiso ea antigen ho HCC.Tlhahlobo ea lintlha tse ngata tsa nucleotide polymorphisms e le 'ngoe lithutong tse 477 e senotse moroalo o tlase ho CNS.Ka lehlakoreng le leng, lihlahala tse sa tsitsang tsa chromosomal tse nang le moroalo o pharalletseng oa CNA li bontšitse matšoao a ho hana 'mele oa ho itšireletsa mafung 'me li amahanngoa le ho ata, ho lokisoa ha DNA, le ho se sebetse ha TP53.Xu et al.e bontšitse hore sehlopha sa HCC se na le lintlha tse phahameng tsa CNA ho feta sehlopha sa lefu la sebete le sa foleng.40 Ho sebelisa tatellano ea liphatsa tsa lefutso tsa sele e le 'ngoe, li-CNA li ile tsa fumanoa li hlaha kapele ho hepatocarcinogenesis 'me li lula li tsitsitse nakong ea tsoelo-pele ea hlahala.41 Chung et al.e fumane hore maemo a cfDNA a phahame haholo ho bakuli ba HCC le hore li-CNA tsa genome-wide ho cfDNA e ne e le letšoao la bohlokoa le ikemetseng le ikemetseng ho bakuli ba HCC ba phekoloang ka sorafenib.42 Bakuli ba nang le moroalo o phahameng oa CNA ba ne ba e-na le monyetla oa ho ba le tsoelo-pele ea mafu le lefu ho feta ba nang le moroalo o fokolang oa CNA.Ollerich le ba bang.e fumane hore kopi ea nomoro ea instability index (CNI) e ka sebelisoa ho lekola CNA ho cfDNA ea bakuli ba mofetše.Ba hlokometse hore bakuli ba nang le mofetše o tsoetseng pele ba ne ba e-na le lintlha tse phahameng haholo tsa CNI ho feta sehlopha sa taolo, se hlahlobang karabelo ea mokuli ho systemic chemotherapy le immunotherapy.43 Liphetho tsena li fana ka maikutlo a hore li-CNA tse fumanoeng ho mehlala ea mokelikeli oa biopsy li ka sebetsa joalo ka matšoao ho bakuli ba nang le mofetše o tsoetseng pele.HCC ka semelo sa phekolo ea tsamaiso.
Hona joale, mekhoa e sebelisoang ho lemoha ctDNA e ka aroloa ka mekhoa e lebisitsoeng le e sa lebelloang.Ka bokhuts'oane, mekhoa e reriloeng joalo ka digital polymerase chain reaction (dPCR), BEAMing digital PCR, Amplification Refractory Mutation System-PCR, Capp-Seq le Tam-Seq li tsotella haholo liphatsa tsa lefutso tse boletsoeng esale pele.Mekhoa e sa lebelloang joalo ka tatellano ea liphatsa tsa lefutso le NGS e fana ka pono e felletseng ea sebopeho sohle sa genomic.44 Ha ho bapisoa le liphanele tse shebiloeng, tatellano ea liphatsa tsa lefutso e ke ke ea bona feela liphetoho tsa lintlha le ho kenya, empa hape le ho hlophisa bocha le ho fapana ha linomoro.prognosis, 'me CTC le cfDNA ke matšoao a matle a ka sebelisoang bakeng sa ho lekola HCC ka matla.45 Ho feta moo, tlhahlobo ea cfDNA e ka ba molemo haholo ho lemoha HCC.Yan et al.e bontšitse hore cfDNA ho plasma ea bakuli ba HCC e ne e phahame haholo ho feta ho bakuli ba nang le sebete sa sebete le taolo e phetseng hantle.Ha ho bapisoa le AFP, ctDNA e lebelletsoe ho ba letšoao le betere la tlhahlobo bakeng sa HCC ea pele.46 Phuputsong e lebelletsoeng ho etsoa ea li-biopsies tsa metsi tse 47 tse ileng tsa etsa liteko tsa cfDNA le protheine sechabeng, li bonts'itsoe li sebetsa hantle ho khetholleng bakuli ba HCC ho bakuli ba se nang HCC.Ka mor'a ho latela bakuli ba 331 ba ultrasound ba tloaelehileng le ba AFP-negative, kutloisiso le ho khetheha ha cfDNA bakeng sa ho hlahloba HCC e ne e le 100% le 94%, ka ho latellana, kahoo cDNA e ne e khona ho lemoha HCC ho batho ba seropositive ba HBsAg.Phuputsong ea Yeo48, khafetsa (92.5%) ea hypermethylation ea mothetsi oa RASSF1A e fumanoe ho bakuli ba HCC.Ho phaella moo, Xu et al.e thehile mohlala oa ho hlahloba ho bolela esale pele HCC ho sebelisa sehlopha sa matšoao a khethehileng a methylation ka ho khetheha le kutloisiso ea 90.5% le 83.3%, ka ho latellana.Sehlopha se lumella bakuli ba HCC hore ba khetholle ho bakuli ba nang le mafu a mang a sebete, a molemo ho feta AFP.Ba boetse ba fumane hore litaolo tse tloaelehileng tse fumanoeng li le ntle li ka ba le mabaka a kotsi bakeng sa HCC, joalo ka tšoaetso ea HBV kapa nalane ea tšebeliso ea joala.25 Re hakanya hore mabaka a kotsi haholo bakeng sa HCC a ka khothaletsa hypermethylation ea cfDNA, eo ka nako eo e tlatsetsang tsoelo-peleng ea HCC, ka hona cfDNA e ka bapala karolo ea bohlokoa ho hlahlobeng lihlopha tse kotsing e kholo.Cai et al.akaretsa mefuta eohle ea liphetoho tsa ctDNA le ho fana ka leano le matla la ho lekola boima ba hlahala ho bakuli.49 Leano lena le ka khetholla tumorigenesis e bohareng ba likhoeli tsa 4.6 pele ho phetoho ea litšoantšo 'me e bontšitse ts'ebetso e phahameng ea ho hlahloba ha e bapisoa le serum biomarkers AFP, AFP-L3, le PIVKA-II.Boleng ba tlhahlobo ea tlhahlobo ea cDNA bo bontšitsoe ha tlhahlobo ea setšoantšo e sa fumanehe, kahoo tlhahlobo ea cDNA e bohlokoa ho fumanoeng HCC ea pele lihlopheng tse kotsing e kholo.Haufinyane tjena, bo-rasaense ba sebelisitse theknoloji ea NGS ho sekaseka matšoao a mefuta e mengata ea liphatsa tsa lefutso (ho kenyeletsoa 5-hydroxymethylcytosine, 5′-motif, fragmentation, nucleosome trace, HIFI) ho disampole tsa kliniki tsa 3204 le cfDNA.Mefuta e 50 e netefalitsoeng hape ea HIFI e nang le literene tse tharo tse ikemetseng, liteko, le li-sete tsa liteko li bonts'itse khethollo e tsitsitseng le e tšepahalang lipakeng tsa HCC le batho bao e seng ba HCC ba nang le kutlo ea 95.79% le 95.42% litekong tse ikhethileng tsa HCC le litekong ka ho latellana.Bong e ne e le 95.00% le 97.83%, ka ho latellana.Boleng ba tlhahlobo ea mokhoa oa HIFI bo phahame ho feta ba AFP ho khetholla HCC ho lefu la ho fokola ha sebete.Ho feta moo, ctDNA e boetse e sebelisoa kalafong ea opereishene.Atsushi et al.e ile ea etsa qeto ea hore boemo ba serum ea ctDNA pele ho ts'ebetso ho bakuli ba HCC 'me ba fumana hore sekhahla sa ho ipheta le sekhahla sa extrahepatic metastasis sehlopheng se setle sa cDNA se ne se phahame haholo ho feta sehlopha se seng se mpe sa cDNA,' me maemo a cDNA a ne a amana haholo.ka tsoelo-pele ea hlahala.51 Kaha ctDNA ke sebali se hlokolosi haholo sa lintho tse phelang, se ka bolela esale pele bokhoni ba HCC ba ho hlasela likepe.Wang et al.e entse tatellano ea liphatsa tsa lefutso tsa bakuli ba 46 ba nang le HCC, 'me tlhahlobo ea mefuta e mengata e bonts'itse hore moeli oa maqhubu a allele a mofuta oa cDNA bakeng sa tlhaselo ea li-microvessels ke 0.83%, sensitivity 89.7% le 80.0%.kotsi e ikemetseng ea tlhaselo ea microvascular ho HCC e ts'oarehang, e fana ka maikutlo a hore cDNA e ka thusa ho tataisa kalafo e nepahetseng.Qetellong, ctDNA e ameha ka botlalo ketsahalong le nts'etsopele ea HCC 'me e ka sebelisoa bakeng sa tlhahlobo ea pele, tlhahlobo ea opereishene le tlhahlobo ea mafu.
Li-CTC ke lisele tse bolaeang tse tsoang lihlahala tse ka sehloohong kapa metastase e senyang mali.Lisele tsa hlahala li hlahisa matrix metalloproteinases (MMPs), e senyang lera le ka tlaase, e lumellang lisele tsa hlahala hore li kene ka ho toba maling le methapong ea lymph.Leha ho le joalo, li-CTC tse ngata li felisoa ka potlako ke anoikis, tlhaselo ea 'mele ea ho itšireletsa mafung, kapa khatello ea ho kuta.53 Phetoho ea epithelial-mesenchymal (EMT) e lumella li-CTC hore li qheleloe ka thoko ho lisele tsa mantlha tsa hlahala, li hlasele li-capillaries, 'me li fumane bophelo bo ntlafetseng, metastasis, invasiveness, le ho hanyetsa lithethefatsi.Liphuputso li bontšitse hore ho na le ho fapana ho tebileng har'a lisele tse fapaneng tsa hlahala ka har'a lihlahala tsa mantlha tsa metastatic.Kahoo, tlhahlobo ea CTC e ka lebisa kutloisisong e felletseng ea tumor cell heterogeneity.54
Matšoao a khethehileng bakeng sa li-CTC tse amanang le HCC li kenyelletsa glypican-3 (GPC3), asialoglycoprotein receptor (ASGPR), epithelial cell adhesion molecule (EpCAM) le stem cell-associated markers tse kang CD44, CD90, 55 le intercellular adhesion molecule 1 (ICAM1).) .56 Lesupa la GPC3 ke protheine e nang le membrane-ankora ea sele e sebelisoang ka bongaka bakeng sa tlhahlobo ea pathological le ho khetholla HCC.57 Pontšo ea GPC3 e tloaelehile haholo liseleng tsa hlahala tsa HCC tse nang le phapang e bohareng le e tlaase 'me e khothalletsa ho falla ha extrahepatic;ho phaella moo, boteng ba GPC3 + ​​CTCs bo bontša metastatic HCC.58 ASGPR ke protheine ea transmembrane e hlahisoang feela holim'a hepatocyte 'me e hlahisoa haholo ka HCC e fapaneng hantle.EpCAM ke e 'ngoe ea liprotheine tse amanang le membrane tse sebelisoang hangata ho tšoara CTC.EpCAM e khethiloe e le letšoao le ka holimo la lisele tsa HCC tse nang le litšobotsi tsa lisele tsa stem, 59 tse amanang le likarolo tse sa tšoaneng tsa kliniki ea HCC, tse kang ho hlaseloa ha methapo ea mali, ho hlahloba maemo a AFP, le boemo bo tsoetseng pele ba kankere ea sebete Sepetlele sa Barcelona (BCLC).Phenotype ea 60 CTC EMT e na le metastatic haholo.Mekhoa ea 54 EMT ho CTC e khothalletsa metastasis ea HCC.Pontšo ea matšoao a EMT a kang vimentin, twist, E-box zinc finger binding (ZEB) 1, ZEB2, snail, slug, le E-cadherin li ithutile li-CTC tse nkiloeng sebeteng ho tsoa ho bakuli ba HCC.58 Sistimi ea CanPatrol™ e ntlafalitsoeng ke Cheng [61] e arotse li-CTC ka lihlotšoana tse tharo tsa phenotypic tse ipapisitseng le matšoao a hlahisoang haholo: epithelial phenotype (EpCAM, CK8/18/19), mesenchymal phenotype (vimentin, coiled), le phenotypes tse tsoakiloeng.Ho bakuli ba 176, kakaretso ea CTC e ne e phahametse AFP ka ho khetholla HCC ho lefu la sebete la sebete.Litekanyetso tsa AUC bakeng sa kakaretso ea CTC, AFP, le kakaretso e kopaneng ea CTC le AFP e ne e le 0.774 (95% CI, 0.704–0.834), 0.669 (95% CI, 0.587–0.750), le 0.821 (95% CI, 0.886-0.786) ).), ka ho latellana.Sehlopha sa CTC se ipapisitseng le EMT se ka bolela esale pele tlhahlobo ea HCC, ho ipheta kapele, metastasis, le nako e khuts'oane ka kakaretso.
Hona joale, mekhoa ea ho lemoha CSC e kenyelletsa mekhoa ea 'mele le mekhoa ea likokoana-hloko.Mekhoa ea 'mele, eo hangata e bitsoang ho ithuisa ho ipapisitse le thepa ea biophysical, haholo-holo e ipapisitse le thepa ea 'mele ea CSC, joalo ka boholo, letsoalo, tefiso, motsamao le ho holofala.Ho itšetlehile ka thepa ea 'mele, ho na le mekhoa e sa tšoaneng e kang litsamaiso tse thehiloeng ho filtration, dielectrophoresis, joalo-joalo. Ea ho qetela, eo hape e tsejoang e le immunoaffinity-based enrichment, e itšetlehile haholo ka ho tlama ha antigen-antibody kaha mokhoa ona o sebelisa li-antibodies khahlanong le li-biomarkers tse khethehileng tsa tumor. tse kang EpCAM, ASGPR, human epidermal growth factor receptor 2 (HER2), prostate specific antigen (PSA), human pancytokeratin (P-CK) le carbamoyl phosphate synthase 1 (CPS1).62 Mofuta o mong, o bitsoang mokhoa oa ho se ruise, o sebelisa cytometry ea phallo ho arola CTCs ho leukocyte ho itšetlehile ka karo-karolelano e phahameng ea nuclear-to-cytoplasmic le boholo.Hajoale, teko e le 'ngoe feela e amohetsoeng ke FDA bakeng sa ho lemoha li-CTC ke sistimi ea Cell-Search™, e sebelisang lesupa la bokaholimo ba lisele tsa EpCAM. Leha ho le joalo, ho fumanoa ha CTC ho itšetlehile ka matšoao a kopantsoeng ho ka eketsa tekanyo ea positivity.54 Motsoako oa li-antibodies khahlanong le ASGPR le CPS1 o fihletse tekanyo ea ho lemoha CTC ea 91% ho bakuli ba HCC.63 Zhang et al o sebelisitse CTC-Chip e nang le li-antibodies khahlanong le ASGPR, P -CK le CPS1, le ho khetholla bakuli ba HCC ho ba nang le lefu la sebete la sebete kapa kankere e seng HCC ka tekanyo ea 100%.64 Phuputso e entsoeng ke Wang e fumane EpCAM + CTCs ho 60% ea bakuli ba 42 HCC 'me e fumane likamano tse kholo pakeng tsa positivity ka bobeli. tekanyo le palo ea li-CTC tse nang le sethala sa TNM.65 Guo et al o fumane hore palo ea PCR e tsoang ho CTC e ne e phahame ho bakuli ba 125/171 (73%) bao boemo ba bona ba AFP bo neng bo le <20 ng / mL ka kutloisiso ea 72.5% le a tse khethehileng tsa 95.0%, ha li bapisoa le 57.0% le 90.0% bakeng sa AFP ho cutoff 20 ng / mL.66 Motsoako oa AFP le CTCs o ka ntlafatsa ho fumanoa ha HCC.45 Ho lumeloa hore li-CTC li na le molemo ho feta AFP nakong ea tlhahlobo ea pele ea lihlopha. e kotsing e kholo ea HCC. Leha ho le joalo, ho fumanoa ha CTC ho itšetlehile ka matšoao a kopantsoeng ho ka eketsa tekanyo ea positivity.54 Motsoako oa li-antibodies khahlanong le ASGPR le CPS1 o fihletse tekanyo ea ho lemoha CTC ea 91% ho bakuli ba HCC.63 Zhang et al o sebelisitse CTC-Chip e nang le li-antibodies khahlanong le ASGPR, P -CK le CPS1, le ho khetholla bakuli ba HCC ho ba nang le lefu la sebete la sebete kapa kankere e seng HCC ka tekanyo ea 100%.64 Phuputso e entsoeng ke Wang e fumane EpCAM + CTCs ho 60% ea bakuli ba 42 HCC 'me e fumane likamano tse kholo pakeng tsa positivity ka bobeli. tekanyo le palo ea li-CTC tse nang le sethala sa TNM.65 Guo et al o fumane hore palo ea PCR e tsoang ho CTC e ne e phahame ho bakuli ba 125/171 (73%) bao boemo ba bona ba AFP bo neng bo le <20 ng / mL ka kutloisiso ea 72.5% le a tse khethehileng tsa 95.0%, ha li bapisoa le 57.0% le 90.0% bakeng sa AFP ho cutoff 20 ng / mL.66 Motsoako oa AFP le CTCs o ka ntlafatsa ho fumanoa ha HCC.45 Ho lumeloa hore li-CTC li na le molemo ho feta AFP nakong ea tlhahlobo ea pele ea lihlopha. kotsing e kholo ea HCC.Leha ho le joalo, ho lemoha ho kopantsoeng ha matšoao a CTC ho ka 'na ha eketsa karolo ea liphello tse ntle.54 Motsoako oa li-anti-ASGPR le li-antibodies tsa CPS1 li fihletse tekanyo ea ho lemoha CTC ea 91% ho bakuli ba HCC.63 Zhang et al.e sebelisitse CTC-Chip e nang le li-antibodies khahlanong le ASGPR, P-CK le CPS1, hape e ile ea khetholla bakuli ba HCC ho ba nang le lefu la sebete la sebete kapa bao e seng HCC ka sekhahla sa 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. khafetsa le palo ea li-CTC tse nang le sethala sa TNM.65 Guo et al o fumane hore PCR e tsoang ho CTCs e ne e phahame ho bakuli ba 125/171 (73%) ba nang le maemo a AFP <20 ng / mL ka kutloisiso ea 72.5% le ho khetheha 95.0% ha e bapisoa le 57.0% le 90.0% bakeng sa AFP boemong bo khaotsoeng ba 20 ng / mL.66 Motsoako oa AFP le CTCs o ka ntlafatsa ho fumanoa ha HCC.45 CTCs ho nkoa e le molemo ho feta AFP nakong ea tlhahlobo ea pele. lihlopha.ka kotsi e kholo ea HCC.Leha ho le joalo, ho lemoha ho kopantsoeng ho ipapisitsoe le matšoao a CTC ho ka eketsa liperesente tsa liphetho tse ntle.54 Motsoako oa li-anti-ASGPR le li-antibodies tsa CPS1 li fihletse tekanyo ea 91% ea ho lemoha CTC ho bakuli ba HCC.63 Zhang et al.e sebelisitse li-chips tsa CTC tse nang le li-antibodies khahlanong le ASGPR, P-CK le CPS1 le bakuli ba khethollang ba nang le HCC ho tsoa ho lefu la sebete le se nang HCC ka 100%.Phuputso ea 64 Wang e supile 60% ea EpCAM+ CTCs ho bakuli ba 42 HCC mme e fumane kamano e kholo lipakeng tsa liketsahalo le palo ea CTCs mothating oa 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，敏感性，敏感性，敏感性，敏感性，敏感性，敏感性，敏感性，敏感性。值为20 ng/mL 时的特异性為57.0% 和90.0%. 65 Guo 等 人 在 在 在 在 <20 n 的5/171 (73%, 为 95.0%, 为 95.0%, 为 95.0%, 为 95.0%, 为 为 患者截止截止 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 的 的 的 的 的 的 的 的 的 的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. e fumane hore ho bakuli ba 125/171 (73%) ba nang le maemo a AFP <20 ng/mL, litekanyetso tsa PCR tse tsoang ho CTC li phahamisitsoe ka kutlo ea 72.5% le tse ikhethang tsa 95.0%, athe AFP e ne e le maemong a ikhethileng. e ne e le 20 ng/mL.ml e ne e le 57.0% le 90.0%.66 Motsoako oa ORP le CTC o ntlafatsa ho lemoha ha HCC.45 CTCs ho nahanoa hore e phahametse AFP tlhahlobong ea pele ea batho ba kotsing e kholo ea HCC.Kahoo, bakeng sa lihlopha tsa HCC tse nang le CTC-positive le tse kotsi haholo, tlhahlobo ea CTC e lokela ho kopanngoa ka tloaelo le ho lemoha ultrasound le AFP.Leha ho le joalo, li-CTC li nkoa e le li-predictors tsa bohlokoa tsa metastasis ea hlahala le ho khutla hape, 'me ho fumanoa ha CTC ha ho khothalletsoe ka boithaopo e le sesebelisoa sa ho hlahloba.62 Ka hona, CTC e ka sebetsa e le biomarker e ntle ea ho bolela esale pele ho feta matšoao a mang a sebelisoang hajoale. Zhou et al o fumane hore bakuli ba nang le lipalo tse phahameng tsa EpCAM + CTCs le lisele tsa T tse laolang li bontšitse kotsi e kholo ea ho hlahisa HCC ho pheta-pheta, ho feta ba nang le palo e tlaase ea CTCs, ka karolelano ea ho khutlela 66.7% vs 10.3% (P <0.001) .67 . Phuputso e tšoanang e tlalehiloe ke Zhong et al.68 Ho phaella moo, Qi e fumane hore 101 ho bakuli ba 112 (90.81%) ba nang le HCC, ho kenyeletsa le ba nang le lefu la pele-pele, ba ne ba le ntle bakeng sa CTCs le hore li-nodule tse nyenyane haholo tsa HCC li ile tsa fumanoa ka mor'a 3. ho isa ho likhoeli tse 5 tsa ho latela. Zhou et al o fumane hore bakuli ba nang le lipalo tse phahameng tsa EpCAM + CTCs le lisele tsa T tse laoloang ba bontšitse kotsi e kholo ea ho hlahisa HCC ho pheta-pheta ho feta ba nang le palo e tlaase ea CTCs, ka karolelano ea ho khutlela 66.7% vs 10.3% (P <0.001) .67 A. phuputso e tšoanang e tlalehiloe ke Zhong et al.68 Ho phaella moo, Qi e fumane hore 101 ea bakuli ba 112 (90.81%) ba nang le HCC, ho kenyeletsa le ba nang le lefu la pele-pele, ba ne ba le ntle bakeng sa CTCs le hore li-nodule tse nyenyane haholo tsa HCC li ile tsa fumanoa ka mor'a 3 ho Likhoeli tse 5 tsa ho latela. Чжоу le др.обнаружили, что у пациентов с повышенным количеством ЦОК EpCAM+ и регуляторных Т-клеток риск развития рецидива ГЦК был выше, чем у пациентов с низким количеством ЦОК, с коэффициентом рецидивов 66,7% против 10,3% (P <0,001)67. Zhou et al o fumane hore bakuli ba nang le EpCAM + CTCs e phahameng le lisele tsa T tse laoloang ba ne ba e-na le kotsi e kholo ea ho khutla ha HCC ho feta ba nang le CTCs e tlaase, ba nang le sekhahla sa 66.7% vs 10.3% (P <0.001) 67.Boithuto bo tšoanang bo ile ba etsoa ke Zhong et al.68. Ho phaella moo, Qi e fumane hore 101 ho bakuli ba 112 (90.81%) ba nang le HCC, ho kopanyelletsa le ba nang le lefu la pele, ba ne ba e-na le li-CTC, le hore li-nodule tse nyenyane haholo tsa HCC li ile tsa fumanoa ka mor'a likhoeli tse 3 ho isa ho tse 5 tsa ho latela. Zhou 等等 - CTC 分别 ​​分别 的 的 的 相比 Zhou 等等 与发现 少与 少风险 少风险 的风险 的风险 的为 的为 的p <0.001)........... Чжоу le 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.ba fumane hore bakuli ba nang le EpCAM + CTCs e phahameng le lisele tsa T tse laoloang ba ne ba e-na le kotsi e kholo ea ho khutla ha HCC ha ba bapisoa le bakuli ba nang le li-CTC tse fokolang, ba nang le litekanyetso tsa ho khutlela ho 66.7% le 10.3%, ka ho latellana (P <0.001).Phuputso e tšoanang e tlalehiloe ke Zhong et al.68 Ho phaella moo, Qi e fumane hore 101 ea bakuli ba 112 HCC (90.81%), ho kopanyelletsa le bakuli ba nang le lefu la pele, ba ne ba e-na le liphello tse ntle tsa CTC 'me ba fumane li-nodule tse nyenyane haholo tsa HCC ka mor'a ho etela 3.Ho shebella ho fihlela likhoeling tse 5.Ba boetse ba fumane li-CTC ho bakuli ba 12 ba nang le tšoaetso e sa foleng ea HBV mme ba fumana lihlahala tse nyane tsa HCC nakong ea likhoeli tse 5 ho bakuli ba 2 ba nang le CTC.69 Ka hona, li-CTC li ka sebelisoa ho bolela esale pele HCC, 70 empa li ka sebelisoa ka tloaelo e le li-biomarker tse boletsoeng esale pele.
Joalo ka cfDNA, cfRNA e lokolloa maling ka litsamaiso tse fapaneng.Limolek'hule tsena tse maling a peripheral li emela lisele tsa mofetše tsa tlhaho.Ha ho bapisoa le matšoao a bonoang ka mekhoa e sa hlaseleng, li-cfRNA li laoloa ka matla, li khethehile ka ho khetheha, 'me li ngata tikolohong e kantle ho sele.Bohlokoa le boleng ba tlhahlobo ea 71 miRNAs (miRNAs) ho HCC bo tlalehiloe lithutong tse ngata.Li-miRNA ke li-RNAs (ncRNAs) tsa khale tse sa ngoliseng likhoutu tse laolang mesebetsi e fapaneng ea limolek'hule ka ho thibela phetolelo ea li-RNAs (mRNAs) tsa manqosa.Li-miRNA li fumaneha ka har'a 'mele ea apoptotic e kentsoeng ka har'a li-exosomes, empa li ka tlama ka mokhoa o tsitsitseng ho liprotheine tsa serum le lipids maling a peripheral mme li ka sebelisoa ho lekola HCC.Li-microRNA li kenya letsoho ntlafatsong ea sebete, lipid metabolism, apoptosis, ho ruruha le nts'etsopele ea HCC.72 Oncogenic miRNAs tse kang miR-21, miR-155 le miR-221 li tsebahala haholo HCC.Haholo-holo, miR-21 e phetha karolo ea bohlokoa ho collagen synthesis ka extracellular matrix le fibrosis le ho khothalletsa hepatocarcinogenesis ka ho kenya lisele tsa stem tsa hematopoietic.72,73 Tumor suppressor miRNAs ho HCC e kenyelletsa miRNA-122, miRNA-29, lelapa la Let-7, le lelapa la miRNA-15.Lelapa la Let-7 le na le li-miRNA tse ngata tsa tumor suppressor tse lebisitseng lelapa la RAS.Lelapa la miR-15 le kenyelletsa miR-15a, miR-15b, miR-16, miR-195, le miR-497, tse nang le tatelano e tlatsanang bakeng sa li-mRNA tse itseng.Ho feta moo, li-RNA tse telele tse sa ngolisoeng (lncRNA) le li-RNA tse chitja (cirRNAs) le tsona li bohlokoa bakeng sa tlhahlobo ea pele ea HCC.Li-lncRNA li emela sehlopha se pharaletseng ka ho fetisisa sa li-ncRNA, ho kenyelletsa le li-ncRNA tse kang mRNA, 'me li ameha ho mafu a mangata a batho.LncRNAs e bapala karolo ea taolo tikolohong ea sebete le lefu le sa foleng la sebete.74 CircRNAs hape ke sehlopha sa li-ncRNA tse nang le mesebetsi e mengata taolong ea polelo ea liphatsa tsa lefutso.Haufinyane tjena, li-circRNA li 'nile tsa nkoa e le lisebelisoa tsa ho hlahloba HCC.
Ho potoloha RNA ea mahala ho na le botsitso bo makatsang, ho kenyelletsa ho hanyetsa mocheso, pH, le RNase, e etsang hore ho itšehla thajana ha fnRNA ho tsoa mali a peripheral ho se ke ha tena ho sebelisa mekhoa e tloaelehileng ea tlhoekiso ea RNA.Mekhoa e sebelisoang haholo e kenyelletsa NGS, microarray le RT-qPCR.NGS e lumella li-microRNA ho lekanngoa ho pholletsa le genome.Leha ho le joalo, mokhoa ona o bitsa chelete e ngata 'me tlhahlobo ha e tloaelehe.Ka lehlakoreng le leng, RT-qPCR ha e theko e tlase, e holisa nucleic acid ka potlako, 'me e fana ka melemo e mengata joalo ka kutlo e phahameng, ho nepahala ho holimo, mefuta e mengata e matla, le ho hloka lisampole tse fokolang.Li-Microarrays ke mokhoa o mong o sebelisoang bakeng sa ho lemoha miRNA ho ipapisitsoe le hybridization e hlokolosi le e ikhethileng ea li-miRNA tse hlakotsoeng ka li-probe tsa DNA tse tlatselletsang, 75 empa tlhahlobo ea data ea microarray e ja nako.
Li-circulating miR-122 le Let-7 li tlalehile hore li ka thusa ho hlahloba HCC ea boemo ba pele lihlopheng tse kotsing e kholo, matšoao ho bakuli ba nang le li-nodule tse amanang le HBV le HCC ea pele.76 Cai et al.e fumane hore litho tsa lelapa la Let-7 (miR-92, miR-122, miR-125b, miR-143, miR-192, miR-16, miR-126, le miR-199a/b) li kotsing ea ho tšoaroa ke lefu le sa foleng. HCC ho bakuli ba nang le lefu la sebete.Lelapa la Let-7 le ka sebetsa e le moemeli ea sebetsang hantle oa biomarker bakeng sa ho bolela esale pele nts'etsopele ea HCC lihlopheng tse kotsi tse amanang le lefu la sebete la C. 77 miR-122 e na le ho nepahala ho phahameng ho hlahloba HCC ho bakuli ba nang le sebete sa sebete.78 Serum e potolohang MiR-107 le eona e hlahlobiloe mekhahlelong ea pele ea HCC, 79 mme e bontšitse bokhoni bo botle ho baahi ba kotsing e kholo.Zhou et al o tlalehile hore sehlopha sa li-miRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a le miR-801) se ka khetholla HCC ho lefu la sebete le sa foleng la B (CHB) le cirrhosis. kutloisiso e ne e le 79.1% le 75%, le ho khetheha 76.4% le 91.1%, ka ho latellana.80 HCC e amanang le HBV, re fumane hore maemo a miR150 a fokotsehile haholo ha a bapisoa le a bakuli ba HBV ba sa foleng ba se nang HCC (sensitivity 79.1%, specificity 76.5%).-224 e ne e phahame ho HCC ha e bapisoa le ho laola bophelo bo botle, 'me litlhahlobo tsa lihlopha tse nyenyane li bontšitse maemo a phahameng ho bakuli ba HCC e amanang le HBV.hepatitis B-associated cirrhosis le bakuli ba HCC ba khethile sehlopha sa siRNA se nang le li-siRNA tse supileng tse hlalositsoeng ka mokhoa o fapaneng tse ka lemohang HCC ka taolo e fapaneng;Lenane la AUC nakong ea tlhahlobo ea pele le molemo ho feta baithaopi ba AFP.Ba fumane hore li-miRNA tse 'nè (miR-1972, miR-193a-5p, miR-214-3p, le miR-365a-3p) li ka khetholla bakuli ba HCC ho bakuli ba se nang HCC.Li-miRNA tse hlano (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p, le miR-148a-3p) li nkoa e le mafu a ka bang teng a HBV ho HCC, cirrhosis le CHB biomarkers, haholo-holo. miR-34a-5p e ka 'na ea e-ba li-biomarker bakeng sa ho thatafala ha sebete,85' me e ka 'na ea e-ba li-biomarker tse ka bang teng bakeng sa tlhahlobo ea pele ea HCC ho batho ba kotsing e kholo.LncRNA e ithutoang ka ho fetisisa ho HCC e sebelisoa haholo mofetšeng oa sebete (HULC).Liphuputso tse ling li bontšitse hore HULC e potolohang ho bakuli ba HCC e ka sebelisoa e le letšoao la ho hlahloba hobane lncRNA ena e laoloa haholo ho bakuli ba HCC ha e bapisoa le batho ba phelang hantle.71,86 Har'a li-lnRNA tse ling, LINC00152 e nkoa e le lncRNA e molemo ka ho fetisisa ea ho hlahloba ka lebaka la AUC e phahameng, kutloisiso le ho khetheha.86 Phuputsong e 'ngoe, polelo ea mali ea peripheral ea LINC00152 e ile ea eketseha butle-butle ho tloha taolong e tloaelehileng ea bophelo bo botle ho ea ho bakuli ba nang le CHB le cirrhosis,' me qetellong ea e-ba holimo ho HCC.Boithuto ba polelo ea circSMARCA5 plasma ea bakuli ba HCC bo bonts'itse ho fokotseha ho tsoelang pele ha polelo ho HCC ho tloha ho lefu la sebete ho isa ho cirrhosis le liso tsa precancerous.87 Tlhahlobo ea li-curve tsa ROC e netefalitse bokhoni ba li-circRNA tsena ho khetholla bakuli ba lefu la sebete kapa sebete sa sebete ho ba nang le HCC, haholo-holo ba nang le maemo a AFP ka tlase ho 200 ng / mL.Ho phaella moo, Zhu o ile a hlahloba 13,617 cyclic RNAs ka lisampole tsa plasma ho tsoa ho bakuli ba HBV ba amanang le HBV 'me a tiisa hore 6 cyclic RNAs e hlalositsoe ka tsela e fapaneng ho HCC le HBV-associated cirrhosis, e fana ka maikutlo a hore cRNAs e ka ba molemo.matšoao bakeng sa tlhahlobo ea pele ea lihlopha tse kotsing e kholo joalo ka tse amanang le lefu la sebete, bakuli ba sclerosis.88
Li-exosomes ke li-membrane vesicles 40-160 nm bophara;li-vesicles tse ngata tsa intracellular li kopana le lera la sele ebe li lokolloa ka har'a matrix a extracellular.Li na le likarolo tse ngata tse sebetsang, tse kenyelletsang lipids, liprotheine, RNA le DNA, 'me li phetha karolo ea bohlokoa puisanong pakeng tsa lisele, lisele tsa HCC le tse seng tsa HCC.Li-Exosomes tsa 89,90 li laola tsoelo-pele ea HCC ka ho kenya tšebetsong li-hepatocyte fibroblasts le lisele tsa stellate, lisele tsa 'mele tsa ho itšireletsa mafung, li-hepatocyte tse tloaelehileng le lisele tsa HCC.91 Sebakeng sa "tumor" microenvironment, lisele tsa tumor li hlahisa palo e kholo ea li-exosomes tse nkiloeng ho tloha liseleng tsa mofetše ho ea liseleng tse sa hōlang, tseo le tsona li amehang ho oncogenesis, degradation, le pontšo ea lisele.92 Liphuputso li bontšitse hore li-exosomes li ka fetisetsa li-oncogenes ho lisele tse tloaelehileng nakong ea mekhoa ea mafu, e ka 'nang ea e-ba e' ngoe ea mekhoa ea tlhaselo ea hlahala le metastasis.93 Karolo ea li-exosomes tsoelo-peleng ea mofetše e ka 'na ea e-ba matla le e tobileng ho mofuta oa kankere, 89 Exosomes e ka kenngoa ka hare ho lisele tse haufi kapa tse hōle ho laola liphatsa tsa lefutso tse ngata ho lisele tse amohelang tse ka' nang tsa ameha ho li-ion tsa puisano tsa intercellular le litšebelisano tsa cellular microenvironment. ho tsamaisana le matšoao a cellular le metabolism.94 Litšobotsi le liphetoho tse matla tsa limolek'hule tsa thepa ea exosome li bonts'a ka ho toba litšoaneleho le liphetoho tse matla tsa lisele tsa hlahala tsa botsoali, 95 eo hape e leng motheo oa tšebeliso ea li-exosomes ha ho hlahlojoa le ho tsebahatsa mofetše, hammoho le ho bolela esale pele karabelo ea motho ka mong kalafong ea anticancer. ..96
Mekhoa e tloaelehileng ea laboratori bakeng sa ho arola le ho hlahloba li-exosomes li rarahane, li na le mehato e mengata, 'me li ja nako, ho kenyelletsa le ultracentrifugation, filtration, size exclusion chromatography, immunoaffinity purification, Western blotting, enzyme-linked immunosorbent assay (ELISA), PCR, le tlhahlobo ea phallo.litsamaiso tse nyane le li-platform tsa lab-on-a-chip tse sebelisang micro/nanotechnology li ntse li ntlafatsoa ka bophara bakeng sa ho arola li-exosome ka potlako, tse loketseng sebakeng sa hau.Nanoparticle tracking analysis (NTA) ke mokhoa o sebelisoang haholo ho khetholla boholo le mahloriso a li-exosomes, ho kenyelletsa le mekhoa e kang magnetic nanoparticles le polyhydroxyalkanoates.Mekhoa ea microfluidic le electrochemical e ka boela ea lemoha ka potlako li-exosomes lihlahisoa tse ngata.
Liprotheine tsa Exosomal ke matšoao a bohlokoa bakeng sa tlhahlobo ea HCC.Phuputsong ea Arbelaiz, boemo ba 98 RasGAP SH3 e tlamang protheine (G3BP) le polymeric immunoglobulin receptor (PIGR) e ne e phahame haholo ho li-exosomes tse nkiloeng ho HCC, 'me katleho e kopantsoeng ea liprotheine tse peli e ne e phahametse ea AFP.Tshepe e ngata haholo ke ntlha ya bohlokwa e tlatsetsang ntshetsopeleng ya HCC.Tseng o tlaleha hore hepcidin e ka bapala karolo ea bohlokoa ho hanyetsa HCC.99 Exosomes e nkiloeng ho sera sa bakuli ba HCC e ne e e-na le kopi e phahameng haholo ea mefuta e fapaneng ea hepcidin mRNA ho feta balekane ba bona ba phetseng hantle, e leng se fanang ka maikutlo a hore hepcidin e ka ba "biomarker" e ncha ea ho hlahloba HCC.Protheine ea 14-3-3ζ ka li-exosomes tse hlahisoang ke 100 HCC e ka fokotsa ts'ebetso ea T cell, ho ata, le ho arohana 'me e ka etsa hore phetoho ea lisele tsa T e be lisele tsa T tse laolang, e leng se etsang hore lisele tsa T li fokotsehe.101 Sena se tšehetsoa ke liphuputso tse 'maloa tse batlisisang ho qoba hlahala ho tsoa ho boits'ireletso ba mmele, 102 e ka kenyang letsoho ho HCC tumorigenesis.
Ntle le boteng ba ecRNA ka har'a plasma kapa serum, li-exosome tse ntlafalitsoeng ke RNA li ka sebelisoa bakeng sa tlhahlobo ea nako ea nnete e sa hlaseleng ha ho hlahlojoa hlahala pele le ho fumana hore na hlahala e bile teng joang le karabelo ea eona kalafong.Boemo ba exosomal miRNA-21 serum ea mali sehlopheng sa HCC e ne e phahame ka makhetlo a 2,21 ho feta sehlopheng sa CHB, 'me sehlopheng sa HCC e ne e le makhetlo a 5.57 ho feta batho ba phelang hantle.Thutong ea Wang, li-exosomes li ekelitse HCC haholo ha li bapisoa le bakuli ba cirrhotic ba nang le boleng ba AUC ba 0.83 (95% CI 0.74-0.93) le 0.94 (95% CI 0.88-1.00).104 Lintlha tse fumanoeng li hlakisitse ho kenya letsoho ha limolek'hule tse khethehileng tsa thepa ea exosomal taolong ea oncogenesis le tsoelo-pele ea HCC.105 Pontšo ea serum ea miR-221, miR-103, miR-181c, miR-181a, miR-93 le miR-26a e lumellana.le metastasis, le maemo a miR21 a ne a phahame haholo ho bakuli ba HCC ho feta ho laola bophelo bo botle le ho bakuli ba CHB.102 LncRNA e ne e e-na le bohlokoa ba ho hlahloba HCC.Liphuputso li bontšitse hore li-exosomes tse nkiloeng ho sera sa bakuli ba HCC li na le litekanyetso tse phahameng haholo tsa LINC00161, LINC000635, le lncRNA e entsoeng ka ho fetola sekhahla sa kholo-β ho feta ho bakuli ba se nang HCC, 'me li-lncRNA tsena li amahanngoa ka matla le sethala sa TNM le molumo oa tumor.110 Conigliaro et al.Li-exosomes tsa CD90 + li ile tsa fumanoa li hlalosa maemo a phahameng a lncRNAH19, e leng se ileng sa eketsa haholo ho lokolloa ha vascular endothelial growth factor (VEGF) le VEGF-R1 receptor tlhahiso, kahoo e susumetsa angiogenesis.93 CircRNAs ke mofuta o mong oa li-ncRNA tsa exosomal - tse hlalositsoeng ka maemo a tlaase empa a tsitsitse ho pholletsa le mefuta eohle, li-circRNAs li boetse li bontša ho khetheha bakeng sa mofuta oa sele, mofuta oa lisele, mohato oa tsoelo-pele le mosebetsi oa taolo.Li-circRNA tse 111 ke li-biomarker tsa tlhahlobo ea mofetše oa pele le o fokolang haholo.112 Liteko tsa morao-rao tsa bongaka li bonts'itse hore ho hlaka ha li-miRNA ka bomong ho boleleng HCC esale pele ha hoa loka.Ka hona, ho lemoha ho rarahaneng ho sebelisa litlhahlobo tse ngata (mohlala, miR-122 le miR-48a hammoho le AFP) ho ka ntlafatsa ho khetholla ha HCC ea pele le ho khetholla HCC ho lefu la ho thatafala ha sebete.100
Bakuli ba nang le CHB le sebete sa sebete ke sehlopha se atileng haholo sa kotsi ea ho hlahisa HCC.Bakeng sa lihlopha tse kotsing e kholo, hang ha karabelo e tsitsitseng ea kokoana-hloko e finyelloa, ho lokela ho etsoa leano la ho lebela le theko e tlaase le itšetlehileng ka kotsi ea HCC, 'me ho hlahlojoa pele ke senotlolo sa ho ntlafatsa ho hlahlojoa le ho phekoloa ha HCC ka tekanyo e phahameng ea litšenyehelo tsa chelete2. ..Mekhoa ea pele ea tlhahlobo ea mofetše e na le mefokolo e mengata: mekhoa e sebetsang ea tlhahlobo ea pele ea mofetše ha e so hlahisoe bakeng sa mefuta e mengata ea mofets'e, 'me ho tšoarella hangata ho tlase.Ha ho bapisoa le mekhoa ea khale ea tlhahlobo ea pele, theknoloji ea biopsy ea metsi e na le melemo e totobetseng: bonolo ba sampole, ho lemoha panrac, ho ikatisa hantle ha sampole, le karabelo e sebetsang ho heterogeneity ea tumor.Ka lebaka la ts'ebeliso e ntle ea litšenyehelo tsa mekhoa e amanang le biopsy ea mokelikeli, ts'ebeliso ea bona tlhahlobong ea HCC ha e so hlahlojoe khafetsa.Leha ho na le tsoelo-pele ea ho lemoha ka nepo boemo ba limolek'hule, biopsy ea mokelikeli e bitsa chelete e ngata ho bona HCC ho bakuli ba shebiloeng, e fokotsa ts'ebeliso ea eona e atileng ha e bapisoa le lits'ebetso tse ikhethileng tsa litšoantšo tse kang ultrasound le imaging resonance magnetic.113,114 Leha ho le joalo, phuputso e fetileng e bontšitse hore biopsy ea metsi e bontšitse molemo o moholo ho latela boleng ba lilemo tsa bophelo (QALYs).115 Melemo ea biopsy ea metsi ka har'a carcinoma ea pele ea mpa le nasopharynx le eona e bontšitsoe.116,117 Pono ea hajoale ke hore biopsy ea mokelikeli e ka tlatselletsa li-biomarker tsa serum le tlhahlobo ea radiological ho hlahlojoe le ho hlahlojoa ha lihlahala.117 118
Ho ea ka lingoliloeng tsa morao-rao, theknoloji ea mokelikeli oa biopsy e bontšitse kutloisiso e phahameng haholo le ho khetheha ha ho hlahlojoa kapele lihlopha tse kotsing e kholo ea kankere ea sebete.Ho sa tsotelehe mofuta oa biopsy ea mokelikeli, e ka khetholla HCC ho batho ba kotsing e kholo ntle le HCC, e fana ka maikutlo a bohlokoa ba tlhahlobo ea kapele kaha phapang lipakeng tsa batho ba kotsing e kholo le ba phetseng hantle e bonahala.ctDNA e na le halofo ea bophelo bo khutšoanyane 'me e ka sebelisoa ho lemoha HCC, kahoo liphetoho leha e le life ho cDNA e entsoeng ka tumor e ka fana ka bopaki ba sebele ba nako ea sebele ea tsoelo-pele ea hlahala, haholo-holo bakeng sa lihlahala tse nyenyane.Boemo bo phahameng ba ctDNA bo bontša tsoelo-pele le ho ata ha mofetše 'me ke sesupo sa pele sa tsoelo-pele le ho ipheta.Ho phaella moo, ho itšetlehile ka liphello tsa ctDNA, bakuli ba ka fumana phekolo ea motho ka mong le ho latela.119 Libaka tse khethehileng tsa methylation e ka ba letšoao le betere ho feta AFP bakeng sa ho tsebahatsa pele HCC le li-nodule tsa cirrhotic.Maemong a ts'oanelang a HCC, maemo a phahameng a cDNA a bonts'a tlhaselo ea microvascular le postoperative recurrence le metastasis.Liphetoho tsa nomoro ea kopi li amahanngoa le ho phela ha bakuli ba HCC.Ho ka nahanoa hore tlhahlobo ea cDNA e kanna ea ameha kalafong e akaretsang ea HCC, 'me cDNA e ka sebetsa e le sesupo se sebetsang sa ho feto-fetoha ha mokhoa oa phekolo.Matšoao a ipapisitseng le liphetoho tse itseng tsa lefutso ho ctDNA a amohetsoe ke litataiso tsa bongaka ho bolela esale pele katleho le ho beha leihlo khanyetso ea lithethefatsi.Teko ea ctDNA e kanna ea ba sesebelisoa se sebetsang sa biopsy sa mokelikeli bakeng sa tlhahlobo ea pele.Li-CTC li boetse li bapala karolo ea bohlokoa tlhahlobong ea pele ea lihlopha tsa HCC tse kotsing e kholo.Matšoao a fapaneng a li-CTC tse amanang le HCC a bohlokoa haholo qalong, nts'etsopele, le ho ipheta hape ha HCC.Joalo ka li-membrane vesicles, li-exosomes li ameha lipuisanong tsa intercellular, haholo liseleng tsa HCC.Li-microRNA tse potolohang li tsitsitse maling 'me kahoo li ka ba molemo bakeng sa tlhahlobo ea pele ea HCC.Butle-butle, liprotheine tsa exosomal le li-exosome tse ruileng tsa RNA li ile tsa sibolloa, 'me katleho ea tsona ea ho bolela esale pele bakeng sa HCC e ile ea tiisoa.Ho khahlisang, maemo a fapaneng a HCC le ona a ka amahanngoa le liphetoho tse fapaneng, kahoo re ka khetha li-biomarker tse fapaneng bakeng sa tlhahlobo ea pele ho latela maemo a fapaneng a HCC.120
Leha ho le joalo, mekhoa ea hajoale ea biopsy ea mokelikeli e belaetsa mabapi le botsitso 'me e ke ke ea khona ho itlhahloba kapa ho lekola HCC kapele, empa e ntse e ka tlatselletsa tlhahlobo le tlhahlobo ea motho ka mong.121 Joalo ka mofuta oa biopsy ea mokelikeli, ho sibolloa le ho nka litšoantšo tsa ctDNA, CTC, cfRNA le AFP e amanang le exosome kapa PIVKA-II li na le ts'ebeliso e ts'episang tlhahlobong ea pele le boits'oaro ba HCC.Leha ho le joalo, mokhoa o nepahetseng oa ho tsoa ha ctDNA maling o ntse o lokela ho hlakisoa.Ho senola lintho tsa mantlha tsa tlhaho tsa ctDNA ho ka thusa ts'ebeliso ea eona joalo ka lesupa.Palo e nyane ea ctDNA e potolohang le litlhoko tse tiileng tsa ho sebetsana le sampole ke liqholotso bakeng sa ts'ebetsong ea tleliniki ea ho lemoha cDNA ho HCC.Ho phaella moo, liphetoho tsa liphatsa tsa lefutso ha li na likarolo tse tobileng tse lumellang ho tsebahatsa ka nepo li-carcinogens.Kaha mefuta e mengata ea liphatsa tsa lefutso le ea somatic le eona e teng lithong tse tloaelehileng, liphetoho tsa lefutso tse hloahloa ka biopsy ea mokelikeli e ka ba thuso e fokolang tlhahlobong ea pele ea HCC.122 Meeli ea liphatsa tsa lefutso tse sebetsang hantle tse hlalositsoeng hantle le li-biomarker tse thusang ho khetholla cDNA ho DNA e seng hlahala ke litaba tsa bohlokoa haholo ts'ebelisong ea cDNA.ho hloka thuso ea matšoao a hlokolosi le a khethehileng bakeng sa ho lemoha li-CTC.Ho ile ha fumanoa feela lisele tse sebetsang tse nang le bokhoni ba metastatic, 'me motsoako o nepahetseng oa matšoao a ntlafalitsoeng a CSC o ne o sa hlaka.Ho itšehla thajana ha li-CTC bakeng sa moetlo le tlhahlobo ea liprofaele tsa tsona tse fetohang le tsona ke mosebetsi o boima.Ka lebaka la mathata a ho tsebahatsa, ho itšehla thajana le ho hloekisoa ha li-exosomes, mokhoa o khethehileng oa molek'hule o ntse o sa hlaka, 'me lithuto tse fetileng mabapi le mochine oa li-exosomes le HCC ha li e-s'o be ka botebo, le tsela eo miRNAs, lncRNAs le liprotheine li arotsoeng ka eona. , 'me ha ho hlake hore na exosome uptake ke mokhoa o itseng oa mofuta.Tšebeliso ea li-exosomes bakeng sa tlhahlobo le kalafo ea HCC e ntse e le sethaleng sa preclinical.Ho haella ha maemo a ts'ebetso ea mokelikeli oa biopsy, joalo ka mofuta oa li-tubes tse sebelisetsoang ho bokella mali, bophahamo ba mali, polokelo ea sampole le ho lemoha, ho itšehla thajana le ho ntlafatsa, ho ka thibela ts'ebeliso ea tsona ts'ebetsong e tloaelehileng ea tleliniki ka lebaka la phapang ea litloaelo litsing tsa bongaka.Ho sebetsa hantle ha biopsy ea metsi tlhahlobong ea pele, tlhahlobo, tlhahlobo ea katleho, le ho bolela esale pele ha HCC ho ntse ho lokela ho hlahlojoa, haholo-holo bakeng sa lihlopha tse kotsing e kholo.Theknoloji ea biopsy ea metsi e na le bokhoni bo boholo 'me ho lebelletsoe hore e tla sebelisoa haholo ts'ebetsong ea bongaka ea mofetše oa sebete haufinyane.
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