期刊
ISCIENCE
卷 24, 期 7, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.102722
关键词
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资金
- Knut och Alice Wallenbergs Stiftelse [CJDB 72110]
- Bash Biotech Inc, San Diego, CA, USA
- SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) [SNIC 2019/3599]
The study stratified ccRCC into three molecular subtypes using systems biology approach, developed biomarkers for patient classification and prognosis prediction, and identified potential drug targets. Mitotane, a repositioned drug targeting SOAT1, showed potential in treating ccRCC based on in vitro experiments.
Clear cell renal cell carcinoma (ccRCC) is the most common histological type of kidney cancer and has high heterogeneity. Stratification of ccRCC is important since distinct subtypes differ in prognosis and treatment. Here, we applied a systems biology approach to stratify ccRCC into three molecular subtypes with different mRNA expression patterns and prognosis of patients. Further, we developed a set of biomarkers that could robustly classify the patients into each of the three subtypes and predict the prognosis of patients. Then, we reconstructed subtype-specific metabolic models and performed essential gene analysis to identify the potential drug targets. We identified four drug targets, including SOAT1, CRLS1, and ACACB, essential in all the three subtypes and GPD2, exclusively essential to subtype 1. Finally, we repositioned mitotane, an FDA-approved SOAT1 inhibitor, to treat ccRCC and showed that it decreased tumor cell viability and inhibited tumor cell growth based on in vitro experiments.
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