Signatures of necroptosis-related genes as diagnostic markers of endometriosis and their correlation with immune infiltration

Abstract

Abstract Background Endometriosis (EMS) occurs when normal uterine tissue grows outside the uterus and causes chronic pelvic pain and infertility. Endometriosis-associated infertility is thought to be caused by unknown mechanisms. In this study, using necroptosis-related genes, we developed and validated multigene joint signatures to diagnose EMS and explored their biological roles. Methods We downloaded two databases (GSE7305 and GSE1169) from the Gene Expression Omnibus (GEO) database and 630 necroptosis-related genes from the GeneCards and GSEA databases. The limma package in Rsoftware was used to identify differentially expressed genes (DEGs). We interleaved common differentially expressed genes (co-DEGs) and necroptosis-related genes (NRDEGs) in the endometriosis dataset. The DEGs functions were reflected by gene ontology analysis (GO), pathway enrichment analysis, and gene set enrichment analysis (GSEA). We used CIBERSORT to analyze the immune microenvironment differences between EMS patients and controls. Furthermore, a correlation was found between necroptosis-related differentially expressed genes and infiltrating immune cells to better understand the molecular immune mechanism. Results Compared with the control group, this study revealed that 10 NRDEGs were identified in EMS. There were two types of immune cell infiltration abundance (activated NK cells and M2 macrophages) in these two datasets, and the correlation between different groups of samples was statistically significant (P < 0.05). MYO6 consistently correlated with activated NK cells in the two datasets. HOOK1 consistently demonstrated a high correlation with M2 Macrophages in two datasets. The immunohistochemical result indicated that the protein levels of MYO6 and HOOK1 were increased in patients with endometriosis, further suggesting that MYO6 and HOOK1 can be used as potential biomarkers for endometriosis. Conclusions We identified ten necroptosis-related genes in EMS and assessed their relationship with the immune microenvironment. MYO6 and HOOK1 may serve as novel biomarkers and treatment targets in the future.