Identification and analysis of novel endometriosis biomarkers via integrative bioinformatics

• Published in: Frontiers in endocrinology (Lausanne) Vol. 13; p. 942368
• Main Authors: Bae, Sung-Jin, Jo, Yunju, Cho, Min Kyoung, Jin, Jung-Sook, Kim, Jin-Young, Shim, Jaewon, Kim, Yun Hak, Park, Jang-Kyung, Ryu, Dongryeol, Lee, Hyun Joo, Joo, Jongkil, Ha, Ki-Tae
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.10.2022
• Subjects: Biomarkers - metabolism; Computational Biology - methods; Endocrinology; endometriosis; Endometriosis - diagnosis; Endometriosis - genetics; Endometriosis - metabolism; Female; Humans; LY96; PDLIM3; Protein Interaction Maps - genetics; PTGIS; TLR4/NF-κB; Wnt Signaling Pathway; Wnt/frizzled; PDLIM3; PTGIS; estrogen receptor; TLR4/NF-κB; Wnt/frizzled; endometriosis; LY96
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2022.942368

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 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 ( , , , , , , and ) out of 17 was validated comparison with external gene sets, and protein expression of four genes ( , , , and ) 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.