ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gynecological Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1577283
This article is part of the Research TopicImmune Predictive and Prognostic Biomarkers in Immuno-Oncology: Refining the Immunological Landscape of CancerView all 22 articles
Stemness-driven clusters in ovarian cancer: immune characteristics and prognostic implications
Provisionally accepted
- 1Chinese Integrative Medicine Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
- 2Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
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Ovarian cancer (OC) is the most common malignant gynecological tumor. Cancer cells with high stemness levels often resist anti-tumor therapies, leading to poor prognosis. However, few studies have systematically classified stemness-related subgroups or explored targeted therapeutic strategies. In this study, stemness-associated genes were identified by comparing transcriptome profiles between adherent and sphere-forming SKOV3 cells. Unsupervised clustering defined distinct stemness-related subgroups in OC patients. Using WGCNA and LASSO regression, we constructed a robust prognostic model and developed a nomogram incorporating clinicopathological factors. The tumor microenvironment (TME), tumor mutation burden (TMB), immune checkpoint profiles, and drug sensitivities were comprehensively analyzed between risk groups. Single-cell RNA-sequencing data revealed that fibroblasts were key contributors to maintaining stemness features.Further in vitro experiments validated that AKAP12 expression correlated with stemness phenotypes. AKAP12 knockdown impaired tumor sphere-formation, reduced migration, and increased cisplatin sensitivity. Immunohistochemical staining of clinical samples and ovarian cancer organoids confirmed the positive association between AKAP12 and the immune checkpoint molecule OX40L.In conclusion, we delineated novel stemness-related gene signatures, accurately predicted recurrence risk and prognosis, and identified AKAP12 as a promising therapeutic target for improving ovarian cancer outcomes.
Keywords: ovarian cancer, Stemness, immune checkpoints, Drug Resistance, Tumor organoid
Received: 15 Feb 2025; Accepted: 27 May 2025.
Copyright: © 2025 Zeng, Wu, Li, Wu, Du and Ping. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Li Ping, Chinese Integrative Medicine Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
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