Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning
Journal article, 2021
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.
bioinformatics
systems biology
cancer systems biology
omics
Author
Xiangyu Li
Royal Institute of Technology (KTH)
Bash Biotech Inc.
Woonghee Kim
Royal Institute of Technology (KTH)
Kajetan Juszczak
Royal Institute of Technology (KTH)
Muhammad Arif
Royal Institute of Technology (KTH)
Yusuke Sato
Institute for the Advanced Study of Human Biology
University of Tokyo
Haruki Kume
University of Tokyo
Seishi Ogawa
Institute for the Advanced Study of Human Biology
Karolinska Institutet
Hasan Turkez
Atatürk University
Jan Borén
Sahlgrenska University Hospital
Jens B Nielsen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
BioInnovation Institute
Mathias Uhlen
Royal Institute of Technology (KTH)
C. Zhang
Zhengzhou University
Royal Institute of Technology (KTH)
Adil Mardinoglu
Royal Institute of Technology (KTH)
King's College London
iScience
25890042 (eISSN)
Vol. 24 7 102722Subject Categories
Cell Biology
Cell and Molecular Biology
Cancer and Oncology
DOI
10.1016/j.isci.2021.102722
PubMed
34258555