Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 10 12 1 18 Xu Wang Department of Gynecology, The First People's Hospital of Wuxue, Wuxue, China Chengri Huang Affiliated Hospital of Yanbian University, Wuxue, China 2026 05 26 2026 06 15 We evaluated whether co-expression of C-terminal tensin-like protein (CTEN/TNS4) and sphingomyelin synthase 1 (SMS1/SGMS1) is associated with epithelial-mesenchymal transition (EMT), platinum resistance, tumor immune features, and outcome in ovarian cancer. This single-center retrospective cohort included 276 patients treated with primary surgery followed by platinum-containing chemotherapy. Immunohistochemistry assessed CTEN, SMS1, EMT markers, and immune-microenvironment markers. Logistic regression and Cox models evaluated platinum resistance and survival. High CTEN and SMS1 expression occurred in 45.7% and 43.1% of tumors, respectively; 28.3% were dual-high. Dual-high expression was associated with advanced FIGO stage, CA125 ≥500 U/mL, ascites, lymph-node metastasis, residual disease ≥1 cm, recurrence/progression, and platinum resistance. It was also associated with low E-cadherin, high N-cadherin and Vimentin, an EMT-high phenotype, low CD8 infiltration, high CD163 infiltration, and higher PD-L1 expression. In multivariable analysis, dual-high expression remained associated with platinum resistance (OR=2.18, 95% CI 1.21–3.94) and shorter PFS (HR=1.52, 95% CI 1.05–2.20). CTEN/SMS1 dual-high expression identifies a clinically adverse ovarian-cancer phenotype associated with EMT, platinum resistance, and relatively immunosuppressive tumor features. These retrospective associations require multicenter and functional validation. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4859 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4859/2441