Integrative bioinformatics analysis of lipid metabolism-related genes and immune infiltration in endometriosis

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Abstract
Endometriosis is referred to as a “benign cancer,” severely impacting women’s reproductive health. However, the pathogenesis of endometriosis remains unclear. This study aims to investigate the potential roles of lipid metabolism-related genes (LMRGs) and immune infiltration in the diagnosis and pathogenesis of endometriosis. Four microarray datasets (GSE6364, GSE51981, GSE153740, and GSE232713) with eutopic endometrium samples of the midsecretory phase were downloaded from the Gene Expression Omnibus database. Seven hundred forty LMRGs were obtained from the Reactome database. The GSE6364 and GSE51981 datasets were merged and differentially expressed genes (DEGs) were identified between endometriosis patients and normal controls. Lipid metabolism-related DEGs were detected by intersecting the DEGs and LMRGs. Functional enrichment analysis, protein–protein interaction analysis, and receiver operating characteristic analysis of lipid metabolism-related DEGs were performed. Additionally, immune cell infiltration was compared between endometriosis patients and normal controls, and associations with lipid metabolism-related DEGs were assessed. Fifty-eight lipid metabolism-related DEGs were identified in endometriosis patients compared with normal controls, which enriched in glycerolipids, fatty acyls, sphingolipids, glycerophospholipids, and sterol lipids metabolism, especially steroid hormone metabolism and arachidonic acid metabolism. Additionally, 11 core genes were identified, with HMGCR and CYP27A1 validated as potential markers for diagnosing endometriosis and assessing its severity, respectively. Immune infiltration analysis revealed that fibroblasts and B lineage cells were predominantly abnormal in the endometrium of the midsecretory phase in endometriosis. Correlation analysis suggested that core genes were closely related to immune cells. In conclusion, HMGCR and CYP27A1 were identified as potential markers for endometriosis and its severity, respectively. Fibroblasts and B lineage cells may significantly contribute to the reduced endometrial receptivity observed in endometriosis. These findings provide new insights into the diagnostic and pathogenic roles of LMRGs in endometriosis and highlight their implications for infertility and pregnancy complications related to endometriosis.
Funding Information
  • Medicine Plus Program of Shenzhen University (2024YG009)
  • Science and Technology Innovation Committee of Shenzhen (JCYJ20230807115108017)

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