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 102722

Ämneskategorier

Cellbiologi

Cell- och molekylärbiologi

Cancer och onkologi

DOI

10.1016/j.isci.2021.102722

Mer information

Senast uppdaterat

2021-07-06