Abstract
Non-homologous End Joining (NHEJ) DNA damage repair pathway is the predominant pathway of DNA double-strand repair in human cells and its aberrant activity is associated with drug resistance in multiple cancers. However, the role of the NHEJ pathway in clear cell type of renal cell carcinoma (ccRCC) has been rarely addressed. We utilized authoritative databases of ccRCC containing multi-omics data, such as mutation, gene expression, DNA methylation, copy number alterations, and high throughput protein estimations to determine alterations in seven core NHEJ genes, including XRCC4, XRCC5, XRCC6, PRKDC, LIG4, NHEJ1, and PAXX. We further determined the association of their expression with clinicopathological features and molecular alterations in ccRCC. A comprehensive analysis of these genes revealed several alterations in the expression of these genes. Interestingly, NHEJ1 is downregulated and associated with better prognosis while PAXX is upregulated in ccRCC and associated with poor prognosis. These results suggest that alterations in DNA repair pathway are common in ccRCC and may provide novel therapeutic opportunities for this malignancy.
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