Prognostic significance of nuclear or cytoplasmic nucleolin expression in human non-small cell lung cancer and its relationship with DNA-PKcs

This study investigated the expression of nucleolin in tissue samples in patients with non-small cell lung cancer (NSCLC). Nucleolin was studied to determine whether it has a prognostic value and if its levels correlate with various clinicopathologic parameters. The relationship between nucleolin and expression of DNA-PKcs was also evaluated. Immunohistochemistry was used for detecting the expression levels of nucleolin and DNA-PKcs in tissues from 225 stage IA to IIIB NSCLC patients who underwent lung surgery. Nucleolin was observed predominantly in the cytoplasm, and some levels were observed in the nucleus. Nucleolin expression was higher in NSCLC tissues than adjacent normal lung tissues. Among 225 NSCLC patients, 117 (52.0 %) had high expression of nucleolin. The expression of nucleolin was significantly associated with pathologic stage (P = 0.013) and T status (P = 0.043). Multivariate analysis revealed that nucleolin, cytoplasmic nucleolin, and nuclear nucleolin expression were independent prognostic factors for both overall survival (OS) (P < 0.001) and disease-free survival (DFS) (P < 0.001). A high level of nuclear nucleolin served as an independent prognostic factor for better survival, while a high level of cytoplasmic nucleolin was closely associated with worse prognosis in NSCLC patients. The expression of nucleolin and cytoplasmic nucleolin positively correlated with DNA-PKcs (P < 0.001). These data suggest that nucleolin could be an effective treatment target and prognostic factor for patients with NSCLC.