PAXX , Not NHEJ1 Is an Independent Prognosticator in Colon Cancer

Frontiers in Molecular Biosciences
Mohit AroraShyam S Chauhan

Abstract

Classical Non-homologous End Joining (NHEJ) pathway is the mainstay of cellular response to DNA double strand breaks. While aberrant expression of genes involved in this pathway has been linked with genomic instability and drug resistance in several cancers, limited information is available about its clinical significance in colon cancer. We performed a comprehensive analysis of seven essential genes, including XRCC5, XRCC6, PRKDC, LIG4, XRCC4, NHEJ1, and PAXX of this pathway, in colon cancer using multi-omics datasets, and studied their associations with molecular and clinicopathological features, including age, gender, stage, KRAS mutation, BRAF mutation, microsatellite instability status and promoter DNA methylation in TCGA colon cancer dataset. This analysis revealed upregulation of XRCC5, PRKDC, and PAXX in colon cancer compared to normal colon tissues, while LIG4 and NHEJ1 (XLF) displayed downregulation. The expression of these genes was independent of age and KRAS status, while XRCC5, PRKDC, and LIG4 exhibited reduced expression in BRAF mutant tumors. Interestingly, we observed a strong association between XRCC6, XRCC5, PRKDC and LIG4 overexpression and microsatellite instability status of the tumors. In multivariate ana...Continue Reading

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Citations

Jul 30, 2021·DNA Repair·Ujjayinee Ray, Sathees C Raghavan

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Methods Mentioned

BETA
affinity purification

Software Mentioned

UALCAN
survminer
Oncomine
Stata
R
UCSC Xena browser
BioPlex
cBioPortal
MEXPRESS
Graphpad Prism

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