Classification of clear cell renal cell carcinoma based on PKM alternative splicing
Journal article, 2020

Clear cell renal cell carcinoma (ccRCC) accounts for 70–80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.

Drug repositioning

Transcriptomics

Systems biology

Biomarker

Alternative splicing

Bioinformatics

Cancer research

PKM

Author

Xiangyu Li

Royal Institute of Technology (KTH)

Beste Turanli

Istanbul Medeniyet University

Kajetan Juszczak

Royal Institute of Technology (KTH)

Woonghee Kim

Royal Institute of Technology (KTH)

Muhammad Arif

Royal Institute of Technology (KTH)

Yusuke Sato

University of Tokyo

Institute for the Advanced Study of Human Biology

Seishi Ogawa

Karolinska Institutet

Institute for the Advanced Study of Human Biology

Hasan Turkez

Erzurum Teknik Üniversitesi

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jan Borén

Sahlgrenska University Hospital

Mathias Uhlen

Royal Institute of Technology (KTH)

C. Zhang

Zhengzhou University

Royal Institute of Technology (KTH)

Adil Mardinoglu

King's College London

Royal Institute of Technology (KTH)

Heliyon

2405-8440 (eISSN)

Vol. 6 2 e03440

Subject Categories

Hematology

Urology and Nephrology

Cancer and Oncology

DOI

10.1016/j.heliyon.2020.e03440

More information

Latest update

3/31/2020