Evidence mapPaperPMID 42499433Full record

ArticleTurkish journal of medical sciences2026

In silico evaluation of the role of PEA3 subfamily ETS transcription factors in chemoresistance in ovarian cancer.

Fevzi Coşkun Sökmen, Laika Kardana, Hikmet Yilmaz, Ahmet Çağlar Özketen, Aynur Karadağ Gürel, Özge Atay, Hasan Hüseyin Kazan

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Article in Turkish journal of medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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7 authors.

Fevzi Coşkun SökmenDepartment of General Internal Medicine, Gülhane Faculty of Medicine, University of Health Sciences, Ankara, Turkiye.ORCID https://orcid.org/0000-0002-5621-8274
Laika KardanaDepartment of Medical Biology, Gülhane Faculty of Medicine, University of Health Sciences, Ankara, Turkiye.ORCID https://orcid.org/0009-0007-1811-4443
Hikmet YilmazDepartment of Medical Biology, Gülhane Faculty of Medicine, University of Health Sciences, Ankara, Turkiye.ORCID https://orcid.org/0000-0002-5108-5900
Ahmet Çağlar ÖzketenDESAM Research Institute, Near East University, Mersin 10, Turkiye.ORCID https://orcid.org/0000-0001-6482-6918
Aynur Karadağ GürelDepartment of Medical Biology, Gülhane Faculty of Medicine, University of Health Sciences, Ankara, Turkiye.ORCID https://orcid.org/0000-0002-5499-5168
Özge AtayDepartment of Biochemistry, Middle East Technical University, Ankara, Turkiye.ORCID https://orcid.org/0009-0002-8601-0295
Hasan Hüseyin KazanDepartment of Medical Biology, Gülhane Faculty of Medicine, University of Health Sciences, Ankara, Turkiye.ORCID https://orcid.org/0000-0001-7936-8606

Funding

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6 · The paper itself

Abstract

Background/aim: The E26 transformation-specific family of transcription factors regulates the cell cycle and apoptosis that are crucial for carcinogenesis. More specifically, the PEA3 subfamily-comprising ETS variant (ETV) transcription factors ETV1, ETV4, and ETV5-has been implicated in multiple oncogenic signaling pathways and chemotherapy resistance. While cisplatin is still a widely used chemotherapeutic treatment for ovarian cancer, its therapeutic efficacy is sometimes limited by the induction of resistance mechanisms. The present study investigates the potential role of PEA3 subfamily genes in cisplatin resistance in ovarian cancer through comprehensive in silico analyses. Materials and methods: Cisplatin response data for ovarian cancer were obtained from the Cancer Treatment Response Database version 2 (CTR-DB2), and the relevant dataset was analyzed. Candidate genes, including members of the PEA3 transcription factor subfamily, were analyzed with a multigene biomarker model, and a receiver operating characteristic analysis was used to measure predictive ability. GEPIA2, KMplotter, and cBioPortal were used for survival analysis, while the TNMplot, cBioPortal, and Clinical Proteomic Tumor Analysis Consortium datasets were used for multiomics characterization and differential expression. Results: The ETV4-CIC gene pair in the CTR-DB2 validation dataset achieved the highest predictive performance for cisplatin response in ovarian cancer with an area-under-curve of 0.939, clearly separating responders from nonresponders. No other gene combinations outperformed this model, demonstrating only moderate predictive capacity. The ETV4-CIC gene pair was also associated with disease-free survival. Differential expression analysis showed downregulation of CIC and upregulation of ETV4 in tumor tissues. Genomic and proteomic analyses confirmed alterations in both genes, while correlation analysis suggested complementary biological roles. Conclusions: The ETV4-CIC gene pair effectively discriminated between cisplatin responders and nonresponders in ovarian cancer. Accordingly, the ETV4-CIC signature may serve as a useful biomarker for cisplatin response prediction and patient stratification in precision oncology.

Indexed as

CisplatinDrug Resistance, NeoplasmOvarian NeoplasmsProto-Oncogene Proteins c-etsTranscription FactorsAntineoplastic AgentsComputer SimulationFemaleHumansAntineoplastic AgentsCisplatinETV4 protein, humanProto-Oncogene Proteins c-etstranscription factor PEA3Transcription FactorsCICcisplatin resistanceETS gene familyETV4Ovarian cancer

Identifiers

PMID42499433
PMCPMC13398591

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.