Identifying Predictive Biomarkers and Immune Infiltration Features in Endometriosis

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This study identified 357 differentially expressed genes and three potential endometriosis biomarkers (PTGIS, EHF, COL10A1) by analyzing GEO datasets and investigating PTGIS's role in cell behavior.

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This paper analyzed transcriptomic data from GEO datasets (GSE104948 and GSE116626) to identify inflammation-related differentially expressed genes between endometriosis and control groups, using limma along with GO/KEGG enrichment via clusterProfiler. It estimated immune cell proportions with CIBERSORT and xCell and assessed correlations between gene expression and immune cell ratios, finding 357 DEGs (136 downregulated, 221 upregulated) with enrichment in adhesion, interleukin-6 response, extracellular matrix-related functions, and protein digestion/absorption pathways. Three genes—PTGIS, EHF, and COL10A1—were highlighted as potential biomarkers, and in 12Z endometriotic epithelial cells PTGIS knockdown reduced viability and increased apoptosis while impairing migration and invasion (with opposite effects from PTGIS overexpression); a key limitation noted by the study is its reliance on bioinformatic analyses across public datasets and in vitro functional validation in a single cell model. This paper is centrally about endometriosis — it identifies and functionally probes PTGIS, EHF, and COL10A1 as inflammation/immune-linked diagnostic and progression biomarkers for endometriosis.

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Abstract

Endometriosis is a common gynecological disorder in which inflammatory and immune responses play a crucial role in its development and progression. This study aimed to identify potential inflammation-related biomarkers for the diagnosis and therapeutic monitoring of endometriosis. Differentially expressed genes (DEGs) between endometriosis and control groups were identified using the limma R package. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the clusterProfiler R package to explore functional categories and biological processes associated with the DEGs. Immune cell proportions were estimated using CIBERSORT and xCell, followed by correlation analysis between gene expression and immune cell ratios. Data were obtained from the GEO datasets GSE104948 and GSE116626. Under the criteria |fold-change (FC)| > 1 and p-value < 0.05, a total of 357 DEGs were identified, including 136 down-regulated and 221 up-regulated genes. GO analysis revealed enriched biological processes, such as regulation of cell-cell adhesion mediated by cadherin, cell-cell adhesion mediated by cadherin, and response to interleukin-6. Functional enrichment included extracellular matrix structural constituents and protein-binding activities. KEGG analysis highlighted pathways related to protein digestion and absorption. Three inflammation-related genes, PGI2 synthase (PTGIS), E26 transformation-specific homologous factor (EHF), and collagen type X alpha 1 (COL10A1), were identified as potential biomarkers for endometriosis. In 12Z endometriotic epithelial cells, PTGIS knockdown reduced viability, enhanced apoptosis, and impaired migration and invasion, whereas PTGIS overexpression had the opposite effects. Collectively, this study suggests that PTGIS, EHF, and COL10A1 may serve as valuable predictors for the progression of endometriosis.
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Abstract

Endometriosis is a common gynecological disorder in which inflammatory and immune responses play a crucial role in its development and progression. This study aimed to identify potential inflammation-related biomarkers for the diagnosis and therapeutic monitoring of endometriosis. Differentially expressed genes (DEGs) between endometriosis and control groups were identified using the limma R package. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the clusterProfiler R package to explore functional categories and biological processes associated with the DEGs. Immune cell proportions were estimated using CIBERSORT and xCell, followed by correlation analysis between gene expression and immune cell ratios. Data were obtained from the GEO datasets GSE104948 and GSE116626. Under the criteria |fold-change (FC)| > 1 and p-value < 0.05, a total of 357 DEGs were identified, including 136 down-regulated and 221 up-regulated genes. GO analysis revealed enriched biological processes, such as regulation of cell-cell adhesion mediated by cadherin, cell-cell adhesion mediated by cadherin, and response to interleukin-6. Functional enrichment included extracellular matrix structural constituents and protein-binding activities. KEGG analysis highlighted pathways related to protein digestion and absorption. Three inflammation-related genes, PGI2 synthase (PTGIS), E26 transformation-specific homologous factor (EHF), and collagen type X alpha 1 (COL10A1), were identified as potential biomarkers for endometriosis. In 12Z endometriotic epithelial cells, PTGIS knockdown reduced viability, enhanced apoptosis, and impaired migration and invasion, whereas PTGIS overexpression had the opposite effects. Collectively, this study suggests that PTGIS, EHF, and COL10A1 may serve as valuable predictors for the progression of endometriosis. Similar content being viewed by others Data Availability Data are available upon reasonable request.

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Qiao D, Liu Y, Lei Y, Zhang C, Bu Y, Tang Y, Zhang Y. rRNA-derived small RNA rsRNA-28S regulates the chemoresistance of prostate cancer cells by targeting PTGIS. Front Biosci (Landmark Ed). 2023;28:102. Funding Not applicable. Author information Authors and Affiliations Contributions XC and LY wrote the manuscript and designed this study. XC, LC, MC, BX, SG, XP, HZ conduced the analysis. All authors approved the final version of the manuscript. Corresponding author Ethics declarations Ethical Approval Not applicable. Consent for Publication Not applicable. Conflict of interest The authors declare no competing interests. Clinical Trial Number Not applicable. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Chen, X., Cheng, L., Cheng, M. et al. Identifying Predictive Biomarkers and Immune Infiltration Features in Endometriosis. Reprod. Sci. 33, 742–757 (2026). https://doi.org/10.1007/s43032-026-02081-z Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-026-02081-z

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Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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