The mechanisms of radiation-induced effects in
cancer mainly involve double-strand breaks (DSBs) which are important in maintaining the stability of genes. The DNA repair genes
breast cancer 1 (BRCA1) and
DNA-dependent protein kinase catalytic subunit (
DNA-
PKcs) are capable of maintaining genetic stability through two distinct and complementary repair mechanisms for
DNA DSBs, known as repair-homologous recombination (HR) and non-homologous end joining (NHEJ).
DNA-
PKcs is a member of the
phosphatidylinositol 3-kinase (PI3K) family. The PI3K/AKT cell signaling pathway is implicated in cell migration and invasion. The
BRCA1 protein is implicated in multiple complex cellular processes that are related to chromosome sensitivity to
mutagens. To determine the
protein expression and clinical implications of
DNA-
PKcs and BRCA1 in
nasopharyngeal carcinoma (NPC) and
cancer progression, we evaluated its expression status by immunohistochemistry in 87 patients who received intensity-modulated
radiation therapy (IMRT). In NPC, negative expression of
DNA-
PKcs was detected in 35 of the 87 (40.2%)
cancer types and was significantly associated with poor patient survival (P<0.05). The overexpression of
DNA-
PKcs and BRCA1 also led to significantly improved distant
metastasis-free survival compared with patients who did not overexpress both genes, although the expression level of BRCA1 and distant
metastasis-free survival were not closely correlated. In addition, multivariate analysis indicated that
DNA-
PKcs status is a predictive marker of distant
metastasis-free survival. In conclusion, lower expression of
DNA-
PKcs may be correlated with higher distant
metastasis in patients with NPC.
DNA-
PKcs may be a predictive marker of distant
metastasis after IMRT, independent of the classical prognostic marker. BRCA1 may additionally exert a synergistic effect to predict distant
metastasis-free survival.