Pan-cancer analysis of human kinome gene expression and promoter dna methylation identifies dark kinase biomarkers in multiple cancers

Siddesh Southekal, Nitish Kumar Mishra, Chittibabu Guda

Research output: Contribution to journalArticlepeer-review

Abstract

Kinases are a group of intracellular signaling molecules that play critical roles in various biological processes. Even though kinases comprise one of the most well-known therapeutic targets, many have been understudied and therefore warrant further investigation. DNA methylation is one of the key epigenetic regulators that modulate gene expression. In this study, the human kinome’s DNA methylation and gene expression patterns were analyzed using the level-3 TCGA data for 32 cancers. Unsupervised clustering based on kinome data revealed the grouping of cancers based on their organ level and tissue type. We further observed significant differences in overall kinase meth-ylation levels (hyper-and hypomethylation) between the tumor and adjacent normal samples from the same tissue. Methylation expression quantitative trait loci (meQTL) analysis using kinase gene expression with the corresponding methylated probes revealed a highly significant and mostly negative association (~92%) within 1.5 kb from the transcription start site (TSS). Several understudied (dark) kinases (PKMYT1, PNCK, BRSK2, ERN2, STK31, STK32A, and MAPK4) were also identified with a significant role in patient survival. This study leverages results from multi-omics data to identify potential kinase markers of prognostic and diagnostic importance and further our under-standing of kinases in cancer.

Original languageEnglish (US)
Article number1189
Pages (from-to)1-17
Number of pages17
JournalCancers
Volume13
Issue number6
DOIs
StatePublished - Mar 2 2021

Keywords

  • Correlation analysis
  • CpG methylation
  • Dark kinase
  • Kinome
  • Pan-cancer
  • Promoter
  • Survival analysis
  • TCGA
  • Understudied kinase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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