1. Molecular Analysis of Short- versus Long-Term Survivors of High-Grade Serous Ovarian Carcinoma
- Author
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Stur, Elaine, Bayraktar, Emine, Dal Molin, Graziela Zibetti, Wu, Sherry Y, Mangala, Lingegowda S, Yao, Hui, Wang, Ying, Ram, Prahlad T, Corvigno, Sara, Chen, Hu, Liang, Han, Tworoger, Shelley S, Levine, Douglas A, Lutgendorf, Susan K, Liu, Jinsong, Moore, Kathleen N, Baggerly, Keith A, Karlan, Beth Y, and Sood, Anil K
- Subjects
Cancer ,Ovarian Cancer ,Genetics ,Biotechnology ,Rare Diseases ,long-term survival ,short-term survival ,ovarian cancer ,HGSC ,TMEM62 ,Oncology and Carcinogenesis - Abstract
Despite having similar histologic features, patients with high-grade serous ovarian carcinoma (HGSC) often experience highly variable outcomes. The underlying determinants for long-term survival (LTS, ≥10 years) versus short-term survival (STS, 2; false discovery rate < 0.01). In the subsequent validation cohort, transmembrane protein 62 (TMEM62) was found to be related to LTS. CIBERSORT analysis showed that T cells (follicular helper) were found at higher levels in tumors from LTS than STS groups. In vitro data using OVCAR5 and OVCAR8 cells showed decreased proliferation with TMEM62 overexpression and positive correlation with a longevity-regulating pathway (KEGG HSA04213) at the RNA level. In vivo analysis using the OVCAR8-TMEM62-TetON model showed decreased tumor burden in mice with high- vs. low-expressing TMEM62 tumors. Our results demonstrate that restoring TMEM62 may be a novel approach for treatment of HGSC. These findings may have implications for biomarker and intervention strategies to help improve patient outcomes
- Published
- 2022