Nuclear Survivin and Its Relationship to DNA Damage Repair Genes in Non-Small Cell Lung Cancer Investigated Using Tissue Array

PURPOSE: To investigate the predictive role and association of nuclear survivin and the DNA double-strand breaks repair genes in non-small cell lung cancer (NSCLC): DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Ku heterodimeric regulatory complex 70-KD subunit (Ku70) and ataxia-telangiectasia mutated (ATM). METHODS: The protein expression of nuclear survivin, DNA-PKcs, Ku70 and ATM were investigated using immunohistochemistry in tumors from 256 patients with surgically resected NSCLC. Furthermore, we analyzed the correlation between the expression of nuclear survivin, DNA-PKcs, Ku70 and ATM. Univariate and multivariate analyses were performed to determine the prognostic factors that inuenced the overall survival and disease-free survival of NSCLC. RESULTS: The expression of nuclear survivin, DNA-PKcs, Ku70 and ATM was significantly higher in tumor tissues than in normal tissues. By dichotomizing the specimens as expressing low or high levels of nuclear survivin, nuclear survivin correlated significantly with the pathologic stage (P = 0.009) and lymph node status (P = 0.004). The nuclear survivin levels were an independent prognostic factor for both the overall survival and the disease-free survival in univariate and multivariate analyses. Patients with low Ku70 and DNA-PKcs expression had a greater benefit from radiotherapy than patients with high expression of Ku70 (P = 0.012) and DNA-PKcs (P = 0.02). Nuclear survivin expression positively correlated with DNA-PKcs (P<0.001) and Ku70 expression (P<0.001). CONCLUSIONS: Nuclear survivin may be a prognostic factor for overall survival in patients with resected stage I-IIIA NSCLC. DNA-PKcs and Ku70 could predict the effect of radiotherapy in patients with NSCLC. Nuclear survivin may also stimulates DNA double-strand breaks repair by its interaction with DNA-PKcs and Ku70.