Identification and analysis of novel endometriosis biomarkers via integrative bioinformatics

Abstract

Endometriosis is a gynecological disease prevalent in women of reproductive age, and it is characterized by the ectopic presence and growth of the eutopic endometrium. The pathophysiology and diagnostic biomarkers of endometriosis have not yet been comprehensively determined. To discover molecular markers and pathways underlying the pathogenesis of endometriosis, we identified differentially expressed genes (DEGs) in three Gene Expression Omnibus microarray datasets (GSE11691, GSE23339, and GSE7305) and performed gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) network analyses. We also validated the identified genes via immunohistochemical analysis of tissues obtained from patients with endometriosis or healthy volunteers. A total of 118 DEGs (79 upregulated and 39 downregulated) were detected in each dataset with a lower (fold change) FC cutoff (log2|FC| > 1), and 17 DEGs (11 upregulated and six downregulated) with a higher FC cutoff (log2|FC| > 2). KEGG and GO functional analyses revealed enrichment of signaling pathways associated with inflammation, complement activation, cell adhesion, and extracellular matrix in endometriotic tissues. Upregulation of seven genes (C7, CFH, FZD7, LY96, PDLIM3, PTGIS, and WISP2) out of 17 was validated via comparison with external gene sets, and protein expression of four genes (LY96, PDLIM3, PTGIS, and WISP2) was further analyzed by immunohistochemistry and western blot analysis. Based on these results, we suggest that TLR4/NF-κB and Wnt/frizzled signaling pathways, as well as estrogen receptors, regulate the progression of endometriosis. These pathways may be therapeutic and diagnostic targets for endometriosis.

Comparative Analysis of Shapley Values Enhances Transcriptomics Insights across Some Common Uterine Pathologies

“…Further, a possible role of the degradation and remodeling of the extracellular matrix in endometriosis datasets has been revealed in our study. Endometriotic tissues have been shown to be significantly associated to extracellular matrix reorganization in some studies, which may explain some of the molecular mechanisms underlying the progression of the disease [47][48][49][50]. Regarding uterine leiomyomas, we were able to detect some significantly enriched biological processes that have been previously reported in association with the disease such as hormone secretion and cell signaling [51].…”

Chronic Pelvic Pain, Vulvar Pain Disorders, and Proteomics Profiles: New Discoveries, New Hopes

“…Bae et al recently identified differentially expressed genes (DEGs) in three gene expression omnibus microarray datasets in endometriotic tissues [44]. In this study, a total of 135 DEGs were detected in each dataset, mostly belonging to signaling pathways associated with inflammation, complement activation, cell adhesion, and the extracellular matrix.…”

Exploration of the shared pathways and common biomarker LY96 in Endometriosis and Systemic lupus erythematosus using integrated bioinformatics analysis

“…Interestingly, it has been shown that LY96 has also been suggested as a diagnostic marker for SLE (37).Likewise, the study concluded that LY96 is believed to have a signi cant impact on in ammatory and immune-related diseases, including rheumatoid arthritis, Crohn's disease, and in ammatory diabetic cardiomyopathy(38-40). Bae et al further veri ed the high expression of the LY96 gene in EMS by immunohistochemistry and western blot analysis, concluded that TLR4/NF-κB and Wnt/frizzled signaling pathways, as well as estrogen receptors, regulate the progression of EMS (41). Bao Guo et al suggested that activation of the TLR4 signaling pathway promotes the recruitment and activation of immune cells, triggering a local in ammatory response, leading to the secretion of in ammatory factors (e.g., TNF-α) and growth factors (e.g., VEGF), which stimulate the proliferation of endometrial cells, invasion, and cause further tissue damage (42).Therefore, we hypothesize that the shared pathogenesis of EMS and SLE is mediated by the TLR4 signaling pathway.…”