Decreased mRNA expression levels of base excision repair (BER) pathway genes is associated with enhanced Ki-67 expression in HNSCC

Abstract

DNA repair system plays an indispensable role in maintaining genomic integrity, and its ability to mediate and repair carcinogen-induced DNA lesion is a key determinant of susceptibility to carcinogenesis. Increasing evidence has demonstrated that reduced DNA repair capacity might play a central role in cancer development. Enhanced proliferation is a hall mark of cancer cells. In this study, we aim to test the association between reduction in DNA repair and enhancement in cell proliferation in HNSCC. The expression of base excision repair pathway genes (XRCC1 and OGG1) and a proliferation marker, Ki-67, was studied in a cohort of 50 HNSCC patients and controls, using real-time PCR in order to determine the potential prognostic significance of these factors. Using real-time PCR, statistically significant downregulation of XRCC1 (p < 0.01) and OGG1 (p < 0.04) was observed in HNC tumor samples compared to control samples. Ki-67 was also overexpressed (p < 0.03) in HNC tumor samples versus control samples. Additionally, to explore gene-gene relationship, we observed a positive Spearmen correlation between XRCC1 versus OGG1 (r = 0.554***, p < 0.0001) and a negative correlation between XRCC1 versus Ki-67 (r = -0.377**, p < 0.007) in HNC cases. OGG1 also showed negative correlation with Ki-67, but this correlation was statistically not significant. In this study, we have found that the deregulation of BER genes (XRCC1 and OGG1) in relation to excessive proliferation (as measured by proliferation marker Ki-67) may be considered as important factors in the development of head and neck cancer in Pakistani population.