Classification of clear cell renal cell carcinoma based on PKM alternative splicing
Artikel i vetenskaplig tidskrift, 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
Författare
Xiangyu Li
Kungliga Tekniska Högskolan (KTH)
Beste Turanli
İstanbul Medeniyet Üniversitesi
Kajetan Juszczak
Kungliga Tekniska Högskolan (KTH)
Woonghee Kim
Kungliga Tekniska Högskolan (KTH)
Muhammad Arif
Kungliga Tekniska Högskolan (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, Biologi och bioteknik, Systembiologi
Jan Borén
Sahlgrenska universitetssjukhuset
Mathias Uhlen
Kungliga Tekniska Högskolan (KTH)
C. Zhang
Zhengzhou University
Kungliga Tekniska Högskolan (KTH)
Adil Mardinoglu
King's College London
Kungliga Tekniska Högskolan (KTH)
Heliyon
24058440 (eISSN)
Vol. 6 2 e03440Ämneskategorier
Hematologi
Urologi och njurmedicin
Cancer och onkologi
DOI
10.1016/j.heliyon.2020.e03440