PRKDC regulates chemosensitivity and is a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients

Abstract

DNA-dependent kinase catalytic subunit (DNA-PKcs) is a critical component of DNA repair machinery and is found to be up- or down-regulated in different cancer types. However, its clinical significance in breast cancer remains unclear. To this end, quantitative PCR was performed to measure PRKDC expression level in 59 pairs of breast cancer tissues and the nontumor adjacent tissues (NATs). The correlation between PRKDC expression and overall survival (OS) as well as the prognostic value of PRKDC were analyzed. In vitro and in vivo effects of PRKDC on chemosensitivity were evaluated in MCF-7 cells. We found that PRKDC expression was significantly increased in breast cancer tissue samples compared with NATs. High PRKDC expression was associated with higher tumor grade (P=0.001), positive lymph node metastasis (P=0.0357) and chemoresistance (P=0.0006). Furthermore, PRKDC expression was significantly correlated with OS in breast cancer patients with (0.0101) or without (P=0.0216) receiving chemotherapy. PRKDC was an independent prognostic factor of OS in breast cancer (P=0.022, hazard ratio=2.69, 95% confidence interval: 1.81-3.84). Moreover, downregulation of PRKDC sensitized MCF-7 cells to chemo-drugs both in vitro and in a xenografted mouse model. Collectively, our study demonstrated that PRKDC is a prognostic biomarker for chemoresistance in breast cancer patients.