Pan-cancer analyses reveal genomics and clinical characteristics of the down regulated genes for recurrent myocardial infarction in cancer
Authors: Wang Zongyu 
Published: February 2022

Backgroun

Early identification of the occurrence and progression of coronary ischemic events is particularly important for the diagnosis and treatment of coronary heart disease complicated with tumor. Therefore, it is of great significance to analyze biomarkers and regulatory factors of recurrent myocardial infarction after first myocardial infarction.In order to specify the regulatory factor of coronary heart disease or myocardial infarction on tumor occurrence and metastasis and clinical survival effect, we select from GEO database for the first time of recurrence after myocardial infarction, myocardial infarction, microarray data set, the comprehensive evaluation of the data set is the key cut genes and cancer, tumor prognosis, the tumor extends into the immune level of mutation, etc.The purpose of this study is to discover the role of myocardial infarction regulatory factors in cancer.

Methods

GSE48060 chip data set was downloaded from GEO database to obtain gene expression profiles of blood samples from normal cardiac function control and first AMI patients within 48 hours after the first myocardial infarction.GEO2R online tool and Excel software were used to screen the differential genes between the reinfarction samples and the normal samples in the GSE48060 chip data set.DAVID database was used for enrichment analysis of GO and KEGG of DEGs.The PPI network was constructed and visualized by Using The STRING database and Cytoscape software, and the key genes were screened by the CytoHubba plug-in of Cytoscape software.TIMER database and GEPIA2 website were used to analyze and verify the expression levels of key genes between tumor tissues and normal tissues in generalized carcinoma.GEPIA2 website was used to analyze the correlation between key genes and tumor prognosis.The correlation between key gene expression and tumor purity and each immune cell was analyzed by TIMER database.CBioPortal website was used to analyze the mutation and correlation of key genes in tumors.

Results

Through analysis, the difference genes of 17 GSE48060 chip data sets of reinfarction samples and normal samples were obtained, and the above genes were all down-regulated genes.Five key genes were obtained through constructing PPI network, which were GART, SOD2, KLRF1, ERAP2 and CXCL5.According to the TIMER result, The expression level of GART in BLCA, BRCA, CHOL, COAD, ESCA, HNSC, KICH, KIRC, LIHC, LUAD, LUSC, PRAD, READ, STAD and THCA was significantly different from that in normal tissues (P < 0.001).The expression levels of SOD2 in BRCA, ESCA, KICH, KIRC, KIRP, LUSC, SKCM and STAD were significantly different from normal tissues (P < 0.001).The expression levels of KLRF1 in BRCA, COAD, HNSC, LIHC, LUAD, LUSC, PRAD, READ, STAD and UCEC were significantly different from those in normal tissues (P < 0.001).The expression levels of ERAP2 in BRCA, KIRC and LUSC were significantly different from those in normal tissues (P < 0.001).The expression levels of CXCL5 in BRCA, COAD, ESCA, HNSC, KICH, KIRC, KIRP, LUAD, LUSC, PRAD, STAD, THCA and UCEC were significantly different from those in normal tissues (P < 0.001).The results of GEPIA2 showed that the expression levels of GART in CESC, CHOL, ESCA, KICH, LUSC, SARC and STAD showed significant differences between tumor tissues and normal tissues (P < 0.05).There were significant differences in the expression levels of SOD2 in BLCA, BRCA, ESCA, PAAD and PCPG between tumor tissues and normal tissues (P < 0.05), and there were significant differences in the expression levels of KLRF1 in LUAD and LUSC between tumor tissues and normal tissues (P < 0.05).There were significant differences in ERAP2 expression between tumor tissues and normal tissues in KICH and LUSC (P < 0.05), and there were significant differences in CXCL5 expression between tumor tissues and normal tissues in CHOL, COAD, ESCA, LUAD, LUSC, READ and STAD (P < 0.05).The results of tumor survival analysis indicated that the correlation between the overall tumor survival (OS) of GART and CESC, KIRC, LUAD, READ and SARC was statistically significant (P < 0.05).The correlation between SOD2 and TUMOR OS of SKCM was statistically significant (P < 0.05).The correlation of TUMOR OS between KLRF1 and HNSC was statistically significant (P < 0.05).The correlation between CXCL5 and TUMOR OS of KICH and KIRC was statistically significant (P < 0.05).There was statistically significant correlation between GART and LUAD’s tumor stage (P < 0.05), SOD2 and SKCM’s tumor stage (P < 0.05), CXCL5 and KICH and KIRC’s tumor stage (P < 0.05).The GART gene expression level is significantly correlated with various immune cells in CESC, KIRC, LUAD, READ and SARC.The expression level of SOD2 gene was significantly correlated with various immune cells in SKCM.The expression level of KLRF1 gene was significantly correlated with various immune cells in HNSC.The expression level of CXCL5 gene was significantly correlated with various immune cells in KICH and KIRC.The proportion of mutations in COAD, KICH, LIHC, READ, SKCM and THCA was the highest, the proportion of amplification in BRCA, ESCA, HNSC, KIRC, LUSC and STAD was the highest, and the proportion of severe deletion in LUAD and PRAD was the highest.

Conclusion

The key down-regulated genes of recurrent myocardial infarction after initial myocardial infarction are related to tumor genesis, metastasis, clinical survival and immune invasion.Key down-regulated genes in recurrent myocardial infarction may serve as important biomarkers for the diagnosis and treatment of cancer.