目的：探讨幽门螺杆菌（Helicobacter pylori, Hp）感染对胃癌细胞共济失调毛细血管扩张突变（ataxia-telangiectasia mutated，ATM）基因表达的影响及其临床意义。方法：从TCGA数据库中获取胃癌相关RNAseq数据，比较ATM基因的表达差 异，分析ATM表达与患者临床病理参数的相关性及预后价值，用Kaplan-Meier法进行生存分析，LinkedOmics数据库分析ATM相 关基因，用R语言进行GO、KEGG富集分析。选用2019年3月至2019年12月贵州医科大学附属医院12例手术切除的胃癌及癌 旁组织标本，以及胃癌细胞系AGS和BGC823，用感染复数40∶1的Hp GZ7菌感染细胞，用免疫组织化学染色法检测胃癌组织中 ATM蛋白的表达，qPCR法检测胃癌组织和细胞中ATM mRNA的表达。结果：TCGA数据显示胃癌和Hp感染胃癌组织中ATM miRNA表达水平均显著高于癌旁组织（均P<0.01)；胃癌组织中ATM miRNA表达与患者的T分期、AJCC分期等病理参数呈正相 关（均P<0.05)，ATM 高表达时生存率显著降低(P<0.05)。实验检测显示，胃癌组织标本中ATM蛋白的表达水平明显高于癌旁 组织(P<0.01)；Hp感染胃癌细胞中ATM miRNA 表达水平显著高于未感染胃癌细胞(P<0.01)。胃癌中ATM基因与NPAT等 12 461个基因呈正相关(P<0.05)，与MIF等7 764个基因呈负相关(P<0.05)。GO、KEGG富集分析显示，ATM富集到DNA修复复 合体、癌症中的转录失调等信号通路。结论：ATM基因在胃癌组织中高表达，患者生存率随表达水平的增高而降低，其与患者的 T分期、AJCC分期等病理参数相关，且Hp感染引起ATM表达水平升高可能是Hp引起胃癌的原因之一。
Objective：To investigate the effect of Helicobacter pylori (Hp) infection on gene expression of ataxia-telangiectasia mutant (ATM) in gastric cancer cells and its clinical significance. Methods: The gastric cancer related RNAseq data was obtained from the TCGA database to compare the differential expressions of ATM. The correlation between ATM expression and clinicopathological parameters as well as the prognostic value of ATM was analyzed. Kaplan-Meier method was used for survival analysis, LinkedOmics database was utilized to analyze ATM-related genes, and R language was used for GO and KEGG enrichment analysis. Twelve pairs of gastric cancer tissues and para-cancerous tissues resected in the Affiliated Hospital of Guizhou Medical University from March 2019 to December 2019 as well as gastric cancer cell lines (AGS and BGC823) were collected for this study. Bacterial Hp GZ7 at a MOI (multiplicity of infection) of 40∶1 was used to infect the cells. The protein expression of ATM in gastric cancer tissues was detected using immunohistochemical staining, and the mRNA expression of ATM in gastric cancer tissues and cells was determined using qPCR. Results: TCGA data showed that the miRNA expression of ATM in gastric cancer tissues and Hp-infected gastric cancer tissues was significantly higher than that in para-cancerous tissues (all P<0.01). The miRNA expression of ATM in the gastric cancer tissues was positively correlated with pathological parameters such as T and AJCC staging (all P<0.05) ; High ATM expression was accompanied with significantly reduced survival rate (P<0.05). Experiment results showed that the protein expression of ATM in gastric cancer tissues was significantly higher than that in para-cancerous tissues (P<0.01)，and the miRNA expression of ATM in Hp-infected gastric cancer cells was significantly higher than that in the uninfected gastric cancer cells (P<0.01). In gastric cancer, ATM gene was positively correlated with 12 461 genes such as NPAT (P<0.05)，and negatively correlated with 7 764 genes such as MIF (P<0.05).The GO and KEGG enrichment analyses showed that ATM is enriched in the pathways such as DNA repair complexes, transcription disorders in cancer. Conclusion: ATM gene is highly expressed in GC tissues, and its high expression results in decreased survival rate of patients. ATM gene is associated with pathological parameters such as patient's T stage and AJCC stage, and the increase in ATM expression level caused by Hp infection may be one of the reasons for Hp caused gastric cancer.
国家自然科学基金资助项目（No.31960028, No.31660031）；贵州省科技基金资助项目（No. 黔科合基础1Z010, No.黔科合基础 1Y333）；贵阳市科技计划项目（筑科合同30-4）