Enhanced expression of the stemness-related factors OCT4, SOX15 and TWIST1 in ectopic endometrium of endometriosis patients

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Endometriotic tissue showed increased expression of stemness-related factors OCT4, SOX15, and TWIST1 compared to the eutopic endometrium in endometriosis patients.

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AI-generated deep summary by claude@2026-06, 2026-06-08

This study analyzed stemness-related markers OCT4, SOX15, TWIST1, and DCAMLK1 in endometrial tissue from 69 women with endometriosis (eutopic/endometriosis patient endometrium) and in 90 samples of endometriotic tissue, compared with control endometrium from 50 women, using immunohistochemistry, qRT-PCR on paired samples, and co-immunofluorescence. The authors found a significant correlation between OCT4 and the stemness-associated markers SOX15 and TWIST1, and they observed co-localization and concordant OCT4/SOX15 expression in epithelial and stromal cells within endometriotic tissue; they also reported that marker expression was not linked to menstrual proliferative/secretory phase in endometriosis patients but differed by cycle phase in controls. A key caveat is that the study relies on semiquantitative immunohistochemical scoring and measurement of marker expression rather than functional assays to prove stem cell activity. This paper is centrally about endometriosis — it examines upregulated stemness-related factors (OCT4, SOX15, TWIST1) in ectopic endometrium and correlates these changes with endometriotic lesion establishment.

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Abstract

BACKGROUND: Current evidence suggests that endometrial-derived stem cells, spilled in the peritoneal cavity via retrograde menstruation, are key players in the establishment of endometriotic lesions. The aim of this study was to determine the presence and distribution of the stemness-related factors OCT4, SOX15, TWIST1 and DCAMLK1 in women with and without endometriosis. METHODS: Immunohistochemical analysis was used to determine stromal and epithelial expression of OCT4, SOX15, TWIST1 and DCAMLK1 in endometriosis patient (EP) endometrium (n = 69) and endometriotic tissue (n = 90) and in control endometrium (n = 50). Quantitative Real-Time PCR of OCT4, SOX15 TWIST1 and DCAMLK1 was performed in paired samples of EP endometrium and endometriotic tissue. Co-immunofluorescence staining was performed for OCT4 and SOX15. For statistical analyses we used unpaired t-test, Fisher combination test and Spearman test. For paired analyses, paired t-test and McNemar test were used. RESULTS: We detected a significant correlation between the expression of the established stem cell marker OCT4 and the stemness-related markers SOX15 (p < 0.001) and TWIST1 (p = 0.002) but not DCAMLK1. We showed a colocalization of SOX15 and OCT4 in epithelial and stromal cells of endometriotic tissue by coimmunofluorescence. A concordant expression of OCT4 and SOX15 in the same sample was observed in epithelial cells of the endometriotic tissue (71.7%). The expression of stemness-related factors was not associated with proliferative or secretory phase of the menstrual cycle in endometriosis patients but was found to be differentially expressed during the menstrual cycle in the control group. Increased expression of epithelial OCT4, SOX15 and TWIST1 was detected in endometriotic tissue compared to EP endometrium in paired (p = 0.021, p < 0.001 and p < 0.001) and unpaired analysis (p = 0.040, p < 0.001 and p = 0.001). CONCLUSION: Our findings support the hypothesis that upregulation of stem cell-related factors contribute to the establishment of endometriotic lesions. TRIAL REGISTRATION: The study was approved by the institutional review board (545/2010 on 6th of May 2014) of the Medical University of Vienna ( http://ethikkommission.meduniwien.ac.at/fileadmin/ethik/media/dokumente/register/alle_2010.pdf ).

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometrium Intracellular Signaling Peptides and Proteins Nuclear Proteins Octamer Transcription Factor-3 Protein Serine-Threonine Kinases RNA, Messenger SOX Transcription Factors Twist-Related Protein 1 Adult Case-Control Studies Doublecortin-Like Kinases Endometriosis Endometriosis Endometrium Female Fluorescent Antibody Technique Humans Immunohistochemistry Intracellular Signaling Peptides and Proteins

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