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The non-coding RNA landscape associated with the malignant transformation of endometriosis into endometriosis-correlated ovarian cancer

ABSTRACT: Background. Endometriosis (EMS) is a chronic, gynecological condition affecting 6-10% of reproductive-age women. While these lesions are benign, ovarian EMS present cancer-like features, and can progress to endometriosis-correlated ovarian cancer (ECOC) through a multistep process. Given the regulatory role of miRNAs in gene expression and biological pathways, we aimed to identify miRNAs associated with the malignant transformation of ovarian EMS, which could serve as a potential diagnostic tool for the early identification of such patients. Methods. Global miRNA profiling was performed in patients with benign ovarian EMS (EMS-b) and patients with ECOC. Differential expression analysis (DEA) of miRNAs between EMS-b, EMS tissues from patients with ECOC (EMS-k) and ECOC tissues was performed. Receiver Operating Characteristic (ROC) curves were built to evaluate the binary classification performance of significant miRNAs. Results. Comparison between EMS-b and EMS-k revealed 13 significantly deregulated miRNAs. Furthermore, when comparing ECOC and EMS-b we observed significant deregulation of 181 miRNAs. ROC analysis revealed a panel of seven upregulated miRNAs with accuracies above 0.7 in identifying EMS-k and EMS-b. Notably, four miRNAs (hsa-miR-200a-3p, hsa-miR-141-3p, hsa-miR-183-5p, hsa-miR-10a-5p) were consistently upregulated in both EMS-k and ECOC tissues. Conclusions. Our study identified a panel of miRNA biomarkers that may serve as potential candidates for the early detection of ECOC in patients previously diagnosed with ovarian EMS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE292134 | GEO | 2025/04/16

REPOSITORIES: GEO

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Project description:Background Reduced endometrial receptivity is a major factor for impaired fertility in endometriosis (EMS). Endometrial deposition of collagen I proteins may account for poor endometrial receptivity in endometriosis. Methods We investigated the expression of collagen I expression in endometrium of endometriosis patients and in constructed EMS mice model. Effect of collagen I on ESCs was evaluated. Co-culture of exosomes with ESCs was conducted to evaluate the uptake of exosomes by different endometrial cell lines and the effect on decidualization of eutopic ESCs and embryo implantation. MiRNA expression profiles were compared between ectopic ESC derived exosomes and eutopic ESC derived exosomes. Luciferase reporter and its mutant plasmids were applied to confirm the direct target of miR-25-3p. Findings Here we found endometrial collagen I deposition with impaired decidualization in endometriosis patients and EMS mice model. Treatment of collagen I with ESCs contributed to impaired decidualization and inhibited BLS expansion in vitro. Endometriotic stromal cell-derived exosomes were detected in eutopic endometrium and the ectopic endometrial stromal cell derived exosomes were more taken-up by the same cell line in eutopic endometrium. Treatment of endometriotic stromal cell-derived exosomes increased the expression of endometrial collagen I in vitro and in vivo, while inhibited BLS expansion. Exosomal miR-25-3p was significantly increased in endometriotic stromal cell-derived exosomes compared with control group, and PTEN is a certain target of miR-25-3p. The promotion of endometrial miR-25-3p significantly increased collagen I expression in vitro through the PTEN/Akt pathway. Interpretation These results suggested that endometriotic stromal cell-derived exosomal miR-25-3p played key role in inducing endometrial collagen I deposition to impair embryo expansion in endometriosis via PTEN/Akt pathway. Funding National Nature Science Foundation of China (82271702), National Natural Science Foundation of China (81771537). Keywords: endometriosis; exosome; collagen I; miRNA; collagen deposition

Project description:BACKGROUND: Endometriosis is a common benign gynaecological disorder. A number of studies have confirmed that the occurrence of disease in endometriosis patients is associated with metabolic changes in biological fluids and tissues. We set out to investigate the metabolic characteristics of follicular fluid in patients with ovarian endometriosis undergoing in vitro fertilization (IVF).METHODS: The current research project is an exploratory cohort study on endometriosis. A total of 19 infertile patients with ovarian endometriosis diagnosed by laparoscopy were enrolled in this study and 23 age- and BMI-matched controls (women with infertility due to male or tubal factors). All the patients underwent IVF treatment with a gonadotropin-releasing hormone antagonist protocol and completed follicular fluid (FF) collection at oocyte retrieval. The metabolomics of FF samples was analyzed by ultra high performance liquid chromatography-orbitrap exploris-mass spectrometer (UHPLC-OE-MS). The best combination of biomarkers was then selected by performing stepwise logistic regression analysis with backward elimination. RESULTS: Fifteen metabolites were identified as biomarkers associated with endometriosis. A final model containing 8-hydroxy-2-deoxyguanosine, biotin, n-acetyl-L-methionine and n-methylnicotinamide was constructed. Receiver operating characteristic analysis confirmed the value of these parameters in diagnosing endometriosis, with a sensitivity of 94.7% and a specificity of 95.7%. Analysis of fortification via the Kyoto Encyclopedia of Genes and Genome showed that 15 metabolites were enriched in 8 metabolic pathways.CONCLUSION: Metabolomics based on UHPLC-OE-MS effectively characterized the metabolomics analysis of FF in patients with ovarian endometriosis. These findings may provide a new basis for a better understanding of how diseases progress and for the discovery of new biomarkers.

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The non-coding RNA landscape associated with the malignant transformation of endometriosis into endometriosis-correlated ovarian cancer

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