ArticleTranslational oncology2026
Integrative transcriptomics and single-cell analysis identify SIX4 as a candidate epithelial target in ovarian cancer and PCOS-associated ovarian dysregulation.
Article in Translational oncology, 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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Abstract
purposeOvarian cancer is a heterogeneous solid tumor, whereas polycystic ovary syndrome (PCOS) is a distinct endocrine-metabolic ovarian disorder. Whether PCOS-associated ovarian dysregulation and ovarian cancer share convergent transcriptomic candidates remains unclear. This study aimed to identify shared transcriptomic candidates and define their cellular localization without implying a causal or clinical comorbidity relationship. MATERIALS AND
methodsPublic bulk transcriptomic datasets from PCOS and ovarian cancer underwent platform-specific preprocessing, within-disease-arm harmonization, differential-expression analysis, robust rank aggregation, and machine-learning-based feature prioritization with SHapley Additive exPlanations. Single-cell RNA sequencing datasets were used to localize prioritized genes in PCOS-related ovarian cell populations and high-grade serous ovarian cancer (HGSOC)-derived compartments. Preliminary validation used DHEA-treated KGN cells and siRNA-mediated SIX4 knockdown in SKOV3 cells. Exploratory docking and molecular dynamics simulation assessed the structural tractability of a SIX4-centered axis.
resultsIntegrated analysis identified shared molecular dysregulation enriched in cell-cycle regulation, chromosome segregation, epithelial remodeling, and Wnt-related pathways. Five candidate genes were prioritized: SIX4, CCNE1, MMP7, KIF2C, and GPX3. SIX4 was the highest-ranked contributor within the computational model. Single-cell analysis showed compartment-specific localization, with SIX4 enriched in HGSOC-derived epithelial populations. DHEA increased SIX4 expression in KGN cells, whereas SIX4 knockdown suppressed SKOV3 proliferation, migration, and colony formation. Molecular dynamics suggested stable predicted engagement between SIX4 and a Benzbromarone-related scaffold.
conclusionThis study identifies SIX4 as a candidate epithelial target in ovarian cancer within a shared, noncausal transcriptomic program associated with PCOS-related ovarian dysregulation.
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