运用组学手段探索EBV相关性与非相关性胃癌的可能差异分子

Exploration of possible different molecules between EBV associated and non-associated gastric cancer by omics

目的运用组学手段探索EBV相关性胃癌(EBVa GC)与EBV非相关性胃癌(EBVn GC)间的分子差异,为EBVa GC治疗选择提供依据。方法显色原位杂交检测胃癌患者手术标本和移植瘤组织EBV RNA状态。靶向捕获测序和蛋白质谱分析EBV阳性和阴性胃癌组织中差异分子,免疫组织化学验证组织中PD-L1的表达。结果与EBVn GC相比,EBVa GC中存在PIK3CA高突变率和TP53低突变率。EBVa GC中转录后调控分子表达上调,而代谢和氧化磷酸化分子下调。PD-L1在EBV阳性移植瘤中表达显著升高(76.92%vs 25.00%;P<0.05)。结论 EBV相关性与非相关性胃癌在基因变异和蛋白表达上存在很大差别。

Objective To identify molecular differences between EBVaGC and EBCnGC by omics to provide a basis for treatment options of EBVaGC.Methods Chromogenic in situ hybridization was used to detect EBV RNA status of surgical specimens and PDXs.Targeted capture sequencing and protein mass spectrometry were implemented to analyze the different molecules,verify the PD-L1 expression by immunochemistry in EBV positive and negative tissues.Results Compared with EBVnGC,the higher PIK3CA mutation rate and lower TP53 mutation rate were found in EBVaGC.Post-transcriptional regulation molecules were up-regulated and molecules associated with metabolism and oxidative phosphorylation were down-regulated in EBVaGC.PD-L1 expression in EBV positive PDXs was significantly higher than that in EBV negative(76.92%vs 25.0%,P<0.05).Conclusions There is a great difference between EBVaGC and EBVnGC on genetic variation and expression,which provides the basis for further exploration of the molecular mechanism and treatment strategy of EBVaGC.