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Clinical Research
Analysis of the expression and clinical significance of ATM in gastric cancer tissues based on bioinformatics data
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Abstract:
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.
Keywords:
gastric cancer ; AGS cell ; BGC823 cell ; ataxia telangiectasia mutant (ATM) gene ; TCGA database ; prognosis
Project Supported:
Project supported by the National Natural Science Foundation of China (No.31960028, No.31660031), the Science and Technology Foundation of Guizhou Province (No.Qiankehe Foundation [2020]1Z010, No.Qiankehe Foundation [2020] 1Y333), and the Guiyang Science and Technology Planning Project (Construction Contract[2017]30-4)
