MAML1与胃癌进展和预后相关性的生物信息学分析

Association between MAML1 and progression,prognosis in gastric cancer based on bioinformatics analysis

目的通过多种生物信息学方法分析MAML1在GC患者中的表达及与临床特征、预后和免疫治疗疗效的相关性。方法利用TCGA数据库分析胃癌组织与正常胃黏膜组织中的MAML1表达水平;Kaplan-Meier在线工具对胃癌数据集GSE15459进行分析,阐明MAML1与患者临床特征及分期、治疗疗效的相关性;STRING软件预测与MAML1表达相关的基因,并用FUNRICH软件评估其富集的分子生物学功能和信号通路;TIMER和GEPIA数据库探索MAML1表达水平与肿瘤浸润免疫细胞及其相应基因标记集之间的关系。结果MAML1在GC组织中的表达水平高于正常组织(P<0.001),且其表达水平与III期、有淋巴结转移、无远处转移的患者生存期相关(P<0.05),而与I、II和IV期、无淋巴结转移和有远处转移的患者生存期无相关性(P>0.05)。MAML1的相关作用基因主要分布在细胞核、参与转录调控,并且主要富集在雄激素受体、C-MYB转录因子和HIF-2α转录调控等相关的信号通路。MAML1表达水平与B细胞、CD4+T细胞、巨噬细胞的表达水平存在正相关关系(P<0.05),但与肿瘤纯度、CD8+T细胞、中性粒细胞、树突状细胞无相关性(P>0.05)。结论MAML1有可能成为GC患者较差的临床预后标志物之一,其潜在分子机制可能与转录调控调节肿瘤微环境有关。

Objective To investigate the expression of MAML1 and its relationship with clinical characteristics,prognosis and the efficiency of immunotherapy in patients with GC.Methods MAML1 expression profile was observed by TCGA database.Kaplan-Meier survival analysis was applied to evaluate the correlation between the expression of MAML1 and clinical characteristics,prognosis and treatment efficiency of patients in GSE15459 dataset.MAML1-associated genes were predicted by STRING and were enriched in GO and KEGG by FUNRICH software.The relationship between MAML1 expression and markers of tumor infiltrated cells were explored by TIMER and GEPIA database.Results MAML1 was abnormally upregulated in GC tissues compared to normal gastric tissues(P<0.001).MAML1 expression was significantly associated with the overall survival of patients in stage III,with lymph node metastasis and without distant metastasis(P<0.001).There was no significant difference between MAML1 expression and the overall survival of patients in stage I,II,IV,without lymph node metastasis and with distant metastasis(P>0.05).MAML1-assoicated genes were mainly located at the nucleus,mediating transcriptional regulation and mainly enriching in androgen receptor,C-MYB transcription factor and HIF-2αtranscription regulation and other related signaling pathways.MAML1 expression was positively related with the expression of B cell,CD4+T cell and macrophages(P<0.05),but without significant difference with tumor purity,CD8+T cell,neutrophils and dendritic cells(P>0.05).Conclusions MAML1 could be used as a marker of clinical prognosis of patients with GC.The potential molecular mechanism might be associated with its function in transcriptional regulation and changes in tumor microenvironment.