Identifying Immune Cell Infiltration and Hub Genes Related to M2 Macrophages in Endometriosis by Bioinformatics...

Endometriosis (EM) is a chronic, estrogen-dependent inflammatory disease. Presently, the pathophysiology of EM is still unclear, and numerous studies have established that the immune system plays a major role in the pathophysiology of EM. Six microarray datasets were downloaded from the GEO public database. A total of 151 endometrial samples (72 ectopic endometria and 79 controls) were included in this study. CIBERSORT and ssGSEA were applied to calculate the immune infiltration of EM and control samples. Moreover, we validated four different correlation analyses to explore immune microenvironment of EM and finally identified M2 macrophage-related hub genes and further conducted the specific immunologic signaling pathway analysis by GSEA. The logistic regression model was investigated by ROC and further validated by two external datasets. From the results of the two immune infiltration assays, we concluded that M2 macrophages, regulatory T cells (Tregs), M1 macrophages, activated B cells, T follicular helper cells, activated dendritic cells, and resting NK cells have a significant difference between control and EM tissues. Through multidimensional correlation analysis, we found that macrophages play an important central role in cell-to-cell interactions, especially M2 macrophages. Four immune-related hub genes, namely FN1, CCL2, ESR1, and OCLN, are closely related to M2 macrophages and play a crucial role in the occurrence and immune microenvironment of endometriosis. The combined AUC of ROC prediction model in test and validation sets were 0.9815 and 0.8206, respectively. We conclude that M2 macrophages play a central role in the immune-infiltrating microenvironment of EM.