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 102722

Subject Categories

Cell Biology

Cell and Molecular Biology

Cancer and Oncology

DOI

10.1016/j.isci.2021.102722

PubMed

34258555

More information

Latest update

7/6/2021 5