Abstract
AimsM2 macrophage is believed to play an important role in the development of endometriosis. This study aimed to identify several key genes related to the M2 macrophage in endometriosis. MethodDifferential expressed genes between endometriosis and non-endometriosis were identified based on three microarray datasets from the Gene Expression Omnibus database. Gene modules significantly associated with M2 macrophage were identified from the weighted gene co-expression network analysis. Furthermore, by intersecting the differential expressed genes and M2 macrophage-associated module genes, M2 macrophage-related genes in endometriosis were identified. Functional analyses of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for these genes were then performed. Following, the least absolute shrinkage and selection operator, random forest, and receiver operating characteristic curves were further conducted to identify the key M2 macrophage-related genes in endometriosis. Finally, the expressions of key genes in endometriosis, as well as their correlations with M2 macrophages were verified in an independent validation cohort. ResultsTotally, 185 M2 macrophage-related genes were identified, and they were mainly enriched in functions associated with the cell cycle, oocyte maturation, and immune response. Following machine learning algorithms, eight key genes were selected in the endometriosis: PGR, OLFM4, PIP5K1B, CCNA1, BRIP1, CADM1, PRAME, and GCNT1. The eight key genes were confirmed to be negative with M2 macrophage infiltration levels. Furthermore, the expression levels of these genes were significantly lower in the middle secretory stage while relevantly higher in the proliferative stage. The validation analysis also showed similar outcomes with the above results. ConclusionEight M2 macrophage-related genes were identified as potential biomarkers of endometriosis, providing novel understanding of immune cells in the endometriosis.
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