TMCO1在胃癌中高表达与患者不良预后相关并通过抑制调亡促进肿瘤恶性进展

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Abstract:ObjectiveToinvestigatetheimpactof highexpresionof transmembraneandcoiledhelixstructuraldomain1 (TMCO1)on prognosis of gastriccancerandthe possible mechanisms.Methods TMCO1 expression in gastriccancerand its efectongastriccancer progresionandprognosis wereanalyzedusingpubliclyavailabledatabasesandclinical dataof patientsundergoigdicalsurgeryinourospitalanditspossibleologicalfunctionswereexploreduingKEGGadGO analyses.Ingastriccancer HGC-27cels,theefectsoflentivirus-mediatedTMCO1overexpressionandTMCO1silncingon cellapoptosis,proliferation,ivasionandmigrationwereexamined.ResultsCOexprsionwassigicantlyeatedin gastriccancertissues (P<0.5),anditshighexpressionwaspositivelycorrlatedwithcancerprogession(P<0anda lowered postoperative 5-yearsurvival rateofthe patients (P<0.05) .Bioinformaticanalysessuggested that TMCO1 mayaffect gastriccancer cellapoptosis via Wntsignaling.InHGC-27cells,TMCO1overexpressionsignificantlypromoted tumorcell proliferation,inibitedcellapoptosis,ndnhancedcellmigrationandinvasion,whereas TCO1silencingproducedthe opposite effects. Western blotting showed that β -catenin levels were significantly upregulated in TMCO1-overexpressing cells anddownregulated incelswithMCO1silencing.ConclusionTMCOlisoverexpressd ingastriccancertissesaditshigh expresionpromotesgastriccancerprogressonandafectslong-termprognosisofthepatients posiblybyactivatingtheWnt/ β -cateninsignalingpathwaytoinhibitapoptosisof gastriccancercells.
Keywords: gastriccancer; transmembrane and coiled-coil domain1; apoptosis; prognosis; Wnt/β-catenin
胃癌在全球的发病率排名第2,死亡率居于第 5[1,2] 尽管一部分早期胃癌患者可以通过手术获得根治,新的放、化疗方案也在不断推陈出新[3-5],但我国胃癌患者的总体生存率仍然仅有 35.2%[6] 。(剩余15127字)