Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning
Artikel i vetenskaplig tidskrift, 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
Författare
Xiangyu Li
Kungliga Tekniska Högskolan (KTH)
Bash Biotech Inc.
Woonghee Kim
Kungliga Tekniska Högskolan (KTH)
Kajetan Juszczak
Kungliga Tekniska Högskolan (KTH)
Muhammad Arif
Kungliga Tekniska Högskolan (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 Üniversitesi
Jan Borén
Sahlgrenska universitetssjukhuset
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
BioInnovation Institute
Mathias Uhlen
Kungliga Tekniska Högskolan (KTH)
C. Zhang
Zhengzhou University
Kungliga Tekniska Högskolan (KTH)
Adil Mardinoglu
Kungliga Tekniska Högskolan (KTH)
King's College London
iScience
25890042 (eISSN)
Vol. 24 7 102722Ämneskategorier
Cellbiologi
Cell- och molekylärbiologi
Cancer och onkologi
DOI
10.1016/j.isci.2021.102722
PubMed
34258555