ERI3在肝癌中高表达并与患者不良预后相关

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Abstract：ObjectiveToanalyze theexpresionpatternofExoribonucleaseFamilyMember3（ERI3）inhepatocelllar carcinoma （HCC）tisuesandits influencesonlong-termprognosisandcancercellmetastasis.MethodsBasedontheTCGALIHC dataset （including 377 HCC and 50 adjacent normal tissues），the differential expressionof ERI3 wasanalyzed using DESeq2，andtheresultswerevalidatedusingimmunohistochemicaldatafromtheHAdatabase.Aprotein-proteininteraction networkwas constructedusing STRINGand GeneMANIA.The prognostic valueofERI3 was assessedbyCoxregresionand Kaplan-Meier（KM）survivalanalyses，itsdiagnosticeficacyevaluatedbyROCcurveanalysisanditscorelationwith immune infiltrationanalyzed withssGSEA algorithm.Anomogramprognostic model was established using multivariate Cox regression.ForfunctionalvalidationofERI3inuitro，ahumanHCCcellineSMMC-7721withERI3knockdownwas constructedtgeinellolifetiogiioesssdng-8looi wound healing，and Transwell assys.Results ERI3 was significantly overexpressed in HCC tissues （ （P<0.001） and its expression levels increased progressively with advanced TNM stages （T1-T4： P<0.001 ）.InHCC patients，high ERI3expressions werecorrelated with a reduced overall survival （HR=2.86， 95% CI： 1.68-4.88; P<0.001 ）， disease-specificsurvival （H=2.27，= 0.013），andprogresso-freeintrval（H=1.83，P012）.DiagnosticeicacyanaysisrvealedanAUCof.955（ 95% CI： 0.931- 0.978）for ERI3.ImmuneinfiltrationstudiesdemonstratedapositivecorelationofERI3expressionlevel withTh2cels（ r= 0.340，P<0.0o1） and a negative correlation with Th17 cells （r=-0.284， P<0.001 ）.Multivariate Cox regression analysis identified ERI3asan independent prognostic factor for HCC （HR=1.987，P-0.003），and theconstructednomogramshowedagood predictiveaccracy（C-index=0.668）.InSMMC-21cells，ERI3knockdownsignificantlysuppressedcellproliferation， migrationdsiossteelllgaoid strongly linked to a poor prognosis of the patients.

Keywords：hepatocellular carcinoma; ERI3;metastasis;prognosis

肝细胞癌（HCC）是一种严重危害人类健康的恶性肿瘤，全球第6大常见恶性肿瘤，也是全球癌症死亡原因中的第3位[12]。（剩余12276字）