Journal article
Molecular Analysis of Short- versus Long-Term Survivors of High-Grade Serous Ovarian Carcinoma
Cancers, Vol.14(4198), p.4198
08/01/2022
DOI: 10.3390/cancers14174198
PMCID: PMC9454595
PMID: 36077735
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, <3 years) are largely unknown. The present study sought to identify molecular predictors of LTS for women with HGSC. A cohort of 24 frozen HGSC samples was collected (12 LTS and 12 STS) and analyzed at DNA, RNA, and protein levels. OVCAR5 and OVCAR8 cell lines were used for in vitro validation studies. For in vivo studies, we injected OVCAR8 cells into the peritoneal cavity of female athymic nude mice. From RNAseq analysis, 11 genes were found to be differentially expressed between the STS and LTS groups (fold change > 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
Details
- Title: Subtitle
- Molecular Analysis of Short- versus Long-Term Survivors of High-Grade Serous Ovarian Carcinoma
- Creators
- Elaine Stur - The University of Texas MD Anderson Cancer CenterEmine Bayraktar - The University of Texas MD Anderson Cancer CenterGraziela Zibetti Dal Molin - Beneficência Portuguesa de São PauloSherry Y. Wu - The University of QueenslandLingegowda S. Mangala - The University of Texas MD Anderson Cancer CenterHui Yao - The University of Texas MD Anderson Cancer CenterYing Wang - The University of Texas MD Anderson Cancer CenterPrahlad T. Ram - The University of Texas MD Anderson Cancer CenterSara Corvigno - The University of Texas MD Anderson Cancer CenterHu Chen - The University of Texas MD Anderson Cancer CenterHan Liang - The University of Texas MD Anderson Cancer CenterShelley S. Tworoger - Moffitt Cancer CenterDouglas A. Levine - Division of Gynecologic Oncology, New York University, New York, NY 11580, USASusan K. Lutgendorf - University of IowaJinsong Liu - The University of Texas MD Anderson Cancer CenterKathleen N. Moore - University of OklahomaKeith A. Baggerly - The University of Texas MD Anderson Cancer CenterBeth Y. Karlan - Department of Obstetrics and Gynecology, University of California, Los Angeles, CA 90095, USAAnil K. Sood - The University of Texas MD Anderson Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.14(4198), p.4198
- DOI
- 10.3390/cancers14174198
- PMID
- 36077735
- PMCID
- PMC9454595
- NLM abbreviation
- Cancers (Basel)
- eISSN
- 2072-6694
- Publisher
- MDPI AG
- Language
- English
- Date published
- 08/01/2022
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
- Record Identifier
- 9984294936102771
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