C-terminal Tensin-like/Sphingomyelin Synthase 1 Co-expression Is Associated with Epithelial-mesenchymal Transition, Platinum Resistance, and an Immunosuppressive Tumor Microenvironment in Ovarian Cancer
Abstract
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.
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| Keywords | ||
| CTEN Epithelial-mesenchymal transition Ovarian cancer Platinum resistance SMS1 SGMS1 TNS4 Tumor immune microenvironment | ||
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