Relationship between insulin resistance and endometrial cancer was revealed by gene screening

Abstract

Background: Epidemiological studies have found, the occurrence of endometrial cancer (EC) is closely related to metabolic diseases, and insulin resistance (IR) plays an important role in the pathogenesis of endometrium, but the specific pathogenesis is still unclear. The purpose of this study is to reveal the relationship between insulin resistance and endometrial carcinoma. Methods: We analyzed one endometrial carcinoma database (GSE106191) and one insulin-resistant database (GSE63992), with GEO database and Venny online analysis tool, and P-value< 0.05 was thought about as statistically significant, then, we found an add-up to 148 different genes. Functional enrichment analysis of these genes using DAVID showed that they were participated in transcription factor activity, signaling pathways and response to factors, etc. Then used Cytoscape to establish Protein-Protein Interaction network, and got 25 hub genes. Then further analyzed the expression differences, histological differences, survival analysis, immune infiltration and genetic alteration of 25 hub genes.Results: Of the 25 hub genes, 9 hub genes (KLF5, BRD4, E2F2, LYN, HES1, YY1, IGSF3, TRAF3 and GJB3) were over-expressed in endometrial carcinoma, 11hub genes (TRO, NEURL2, PTEN, RARA, RYBP, OGT, FBXW7, PIK3C3, PIK3C2B, ING3 and DDX58) were under-expressed, and there were no significant difference among 5 hub genes (MYL12A, RAD21, TGFBRAP1, IRAK2 and PTPN1).The results showed that the survival time of patients expressing OGT, IGSF3, TRO, NEURL2 and PIK3C2B may be significantly and closely related to EC, and the percentage of gene changes of five central genes ranged from 3% to 10% of a single gene, was also related to the infiltration of seven kinds of immune cells in endometrial carcinoma.Conclusion: The five key genes (OGT, IGSF3, PIK3C2B, TRO and NEURL2) may be involved in immune infiltration in the progression of endometrial carcinoma, and there is also a certain mutation probability in gene mutation. Insulin resistance may be a trigger in the pathogenesis of endometrial cancer.