Discovery of Functional Alternatively Spliced PKM Transcripts in Human Cancers

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 transcripts encoding PKM2, and three previously unstudied transcripts, namely ENST00000389093, ENST00000568883 and ENST00000561609, exhibited opposite prognostic indications in different cancers. Moreover, we validate the prognostic effect of these transcripts in an independent kidney cancer cohort. Finally, we reveal that ENST00000389093 and ENST00000568883 possess pyruvate kinase enzymatic activity and could have functional roles in metabolism, cell invasion and hypoxia response in cancer cells. Our study provided a potential explanation to the controversial prognostic indication of PKM, and could invoke future studies focusing on revealing the biological and oncological role of these alternative spliced variants of PKM.