Prognostic and potential therapeutic roles of PRKDC expression in lung cancer

Abstract PRKDC is a key factor involved in the ligation step of the non-homologous end joining pathway. Its dysfunction has proven to be a biomarker for radiosensitivity of cancer cells. Our previous study has shown that PRKDC mutations is associated with tumor immune response. However, the prognostic value of PRKDC at transcriptome levels and the underlying mechanisms have not been clarified yet. In this study, we analyzed the PRKDC mRNA levels in pan-cancer datasets and examined its prediction value in prognosis, immunotherapy and chemotherapeutic responses. We found that PRKDC overexpression is a risk factor for many cancers and is correlated with immunotherapy resistance. It is also significantly related to homologous recombination deficiency. As the results are remarkably significant in lung cancer, we therefore further confirmed the antitumor efficacy of PRKDC inhibitors alone or combine with cisplatin in vitro in human lung cancer cells. This study demonstrated that PRKDC is a potential prognostic biomarker, immunotherapy target, and promising combination candidate for PARP inhibitors and cisplatin respectively, in human cancers, particularly for lung cancer, and highlight the potential of PRKDC targeted inhibitors for treatment of lung cancer.