外周血ASH1L和PFAS m6A修饰作为胃癌新型生物标志物的临床价值及分子机制研究

外周血特定mRNA m6A有望成为胃癌（GC）新型生物标志物。我们前期研究发现GC患者外周血总RNA m6A水平显著升高，具有重要诊断价值；然而其作为GC生物标志物缺乏特异性，特定mRNA m6A是否较总RNA m6A更具价值尚待研究。我们新近研究发现：淋巴细胞PENG-EBV与GC细胞共培养后，其转录组m6A谱明显改变；ASH1L、PFAS m6A修饰在PENG-EBV细胞及GC患者外周血中均显著上调；探索队列ROC曲线分析结果表明ASH1L、PFAS m6A的诊断效能优于总RNA m6A。据此提出假说：外周血ASH1L、PFAS m6A可作为潜在的GC新型生物标志物。为验证假说，本研究拟通过临床标本、细胞及动物研究，进一步明确外周血ASH1L、PFAS m6A作为GC新型生物标志物的临床价值，初步阐明导致其变化的分子机制，为GC诊断、病程监控、疗效跟踪及预后判断提供新的策略和理论依据。

Specific mRNA m6A in peripheral blood possess the potential as novel biomarker for gastric cancer (GC). In our previous study, we found that the levels of total RNA m6A in peripheral blood were significantly increased in GC patients, which was valuable for GC diagnosis, but lack of specificity as GC biomarker. Whether specific mRNA m6A is more valuable than total RNA m6A in peripheral blood still needs further study. Our recent studies have shown the m6A maps of transcriptome for lymphocytes (PENG-EBV) were markedly altered after co-cultured with GC cells. ASH1L and PFAS m6A were significantly up-regulated in PENG-EBV cells and peripheral blood of GC patients. ROC curve analysis based on the discovery cohort showed that the diagnostic efficacies of ASH1L and PFAS m6A were better than that of total RNA m6A. Consequently, we speculated that ASH1L and PFAS m6A in peripheral blood may possess the potential as novel biomarkers for GC. To verify this hypothesis, we will further assess the clinical values of ASH1L and PFAS m6A as novel biomarkers for GC, preliminarily ascertain the corresponding molecular mechanisms by conducting the clinical specimens, cellular and animal studies, ultimately providing a novel strategy and theoretical basis for diagnosis, monitoring, follow-up of curative efficacy and prognosis of GC.