Discovery of functional alternatively spliced PKM transcripts in human cancers
Xiangyu Li, Cheng Zhang, Woonghee Kim, Muhammad Arif, Chunxia Gao, Andreas Hober, David Kotol, Linnéa Strandberg, Björn Forsström, Åsa Sivertsson, Per Oksvold, Morten Grøtli, Yusuke Sato, Haruki Kume, Seishi Ogawa, Jan Boren, Jens Nielsen, Mathias Uhlen, Adil Mardinoglu
Received Date: 15th May 19
The association of pyruvate kinase muscle type (PKM) with survival of cancer patients is controversial. Here, we focus on different transcripts of PKM and investigate the association between their mRNA expression and the clinical survival of the patients in 25 different cancers. We find that the transcript encoding PKM2, and three other functional transcripts are prognostic in multiple cancers. Our integrative analysis shows that the functions of these four transcripts are highly conservative in different cancers. Next, we validate the prognostic effect of these transcripts in an independent kidney renal clear-cell carcinoma (KIRC) cohort and identify a prognostic signature which could distinguish high- and low-risk KIRC patients. Finally, we reveal the functional role of alternatively spliced PKM transcripts in KIRC, and discover the protein products of different transcripts of PKM. Our analysis demonstrated that alternatively spliced transcripts of not only PKM but also other genes should be considered in cancer studies, since it may enable the discovery and targeting of the right protein product for development of the efficient treatment strategies.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.