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Classification of clear cell renal cell carcinoma based on PKM alternative splicing

Xiangyu Li, Beste Turanli, Kajetan Juszczak, Woonghee Kim, Muhammad Arif, Yusuke Sato, Seishi Ogawa, Hasan Turkez, Jens Nielsen, Jan Boren, Mathias Uhlen, Cheng Zhang, Adil Mardinoglu
doi: https://doi.org/10.1101/823336
Xiangyu Li
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
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Beste Turanli
2Department of Bioengineering, Istanbul Medeniyet University, Istanbul, Turkey
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Kajetan Juszczak
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
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Woonghee Kim
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
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Muhammad Arif
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
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Yusuke Sato
3Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan
4Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Seishi Ogawa
3Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan
5Department of Medicine, Centre for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden
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Hasan Turkez
6Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum 25240, Turkey
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Jens Nielsen
7Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
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Jan Boren
8Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital Gothenburg, Sweden
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Mathias Uhlen
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
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Cheng Zhang
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
9School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China
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  • For correspondence: adilm@scilifelab.se cheng.zhang@scilifelab.se
Adil Mardinoglu
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
10Centre for Host–Microbiome Interactions, Dental Institute, King’s College London, London, SE1 9RT, United Kingdom
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  • For correspondence: adilm@scilifelab.se cheng.zhang@scilifelab.se
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Summary

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 12, 2019.
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Classification of clear cell renal cell carcinoma based on PKM alternative splicing
Xiangyu Li, Beste Turanli, Kajetan Juszczak, Woonghee Kim, Muhammad Arif, Yusuke Sato, Seishi Ogawa, Hasan Turkez, Jens Nielsen, Jan Boren, Mathias Uhlen, Cheng Zhang, Adil Mardinoglu
bioRxiv 823336; doi: https://doi.org/10.1101/823336
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Classification of clear cell renal cell carcinoma based on PKM alternative splicing
Xiangyu Li, Beste Turanli, Kajetan Juszczak, Woonghee Kim, Muhammad Arif, Yusuke Sato, Seishi Ogawa, Hasan Turkez, Jens Nielsen, Jan Boren, Mathias Uhlen, Cheng Zhang, Adil Mardinoglu
bioRxiv 823336; doi: https://doi.org/10.1101/823336

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