Evaluation of Genes and Molecular Pathways Involved in the Switch of Endometriosis to Ovarian Cancer: A Systems Biology Approach

In: Indian Journal of Gynecologic Oncology · 2025 · vol. 23(2) · doi:10.1007/s40944-025-01010-3 · W4410378032
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This study identified 311 genes common to endometriosis and ovarian cancer, revealing eight hub genes including STAT3, TP53, and RELA, with hsa-miR-146a-5p and RELA showing significant interactions.

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This systems biology paper investigated genes and molecular pathways potentially involved in progression from endometriosis to ovarian cancer by integrating ovarian cancer and endometriosis gene sets from GenCLip3 and DisGeNET, then running protein–protein interaction and hub-gene analyses via STRING, Cytoscape, and the CytoHubba plugin. They identified 311 shared genes and highlighted eight hub genes (STAT3, TP53, SRC, PIK3CA, JUN, CTNNB1, ESR1, RELA), with hsa-miR-146a-5p showing the most miRNA–hub gene interactions and RELA showing the most transcription factor interactions. The authors reported that TP53, RELA, IL-6, and STAT3 had the strongest correlations with ovarian cancer based on Comparative Toxicogenomics Database scores, while noting the work is a review/in silico analysis without original patient or animal experiments. This paper is centrally about endometriosis — focusing on gene and pathway modeling of the “switch” from endometriosis to ovarian cancer.

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Abstract

Background In this study, we investigated the genes and pathways associated with the progression of endometriosis to ovarian cancer (OC).

Materials and methods

We utilized the GenCLip3 and DisGeNET databases to identify genes related to OC and endometriosis. Protein–protein interaction analysis of the common genes was performed using the STRING database, and visualization was achieved through Cytoscape. The Cytohubba plugin of Cytoscape was employed to determine hub genes. Transcription factors (TFs) and microRNAs (miRNAs) targeting the hub genes were identified using the miRTarBase and ChEA databases, linked to the Enrichr software. Furthermore, we investigated and analyzed the hub genes associated with ovarian cancer risk using the Comparative Toxicogenomics Database.

Results

Through the GenCLip3 and DisGeNET databases, we identified 311 genes shared between OC and endometriosis. Analysis of the protein–protein interaction network and hub gene identification revealed eight hub genes: STAT3, TP53, SRC, PIK3CA, JUN, CTNNB1, ESR1, and RELA. Among the miRNAs, hsa-miR-146a-5p exhibited the most interactions with the hub genes, while RELA showed the highest number of interactions among the TFs. Finally, our findings demonstrated that TP53, RELA, IL-6, and STAT3 exhibited the strongest correlations with ovarian cancer, as indicated by their high scores.

Conclusion

In conclusion, the hub genes identified in this study are involved in the progression of endometriosis to OC. Understanding the associated upstream and downstream pathways can aid in the development of targeted treatment strategies and improve the survival outcomes for patients. Similar content being viewed by others Data Availability This is a review study, and it is not an original. Data availability is corresponding author responsibility.

References

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Acknowledgements

The authors appreciate and thank the efforts of the Center for the Development of Clinical Researches of the Educational and Therapeutic Research Complex of Birjand University of Medical Science. Funding None. Author information Authors and Affiliations Corresponding authors Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Ethical Approval This article does not contain any studies with human participants or animals performed by any of the authors. Consent for Publication 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 Zarifi, N., Fateh, A., Fazeli, R. et al. Evaluation of Genes and Molecular Pathways Involved in the Switch of Endometriosis to Ovarian Cancer: A Systems Biology Approach. Indian J Gynecol Oncolog 23, 78 (2025). https://doi.org/10.1007/s40944-025-01010-3 Received: Revised: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s40944-025-01010-3

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