Clinicopathologic features and prognostic implications of NOK/STYK1 protein expression in non-small cell lung cancer

Background: The expression of novel oncogenic kinase (NOK), a member of the protein tyrosine kinase (PTK) family, has been observed in several human malignancies including non-small cell lung cancer (NSCLC). However, the clinic relevance of NOK expression in NSCLC remains unclear. Methods: In this study, NOK expression in tumor cells was assessed using immunohistochemical methods in 191 patients with resected NSCLC. The association of NOK expression with clinicopathological parameters, including the Ki-67 labeling index (LI), was also evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of NOK expression on survival. Results: Data showed that NOK was expressed in 75.4% and 14.1% of cancer lesions and corresponding adjacent non-cancerous tissue, respectively. Out of all the clinicopathological factors analyzed, NOK expression was significantly correlated with the grade of tumor differentiation (P = 0.035), pTNM stage (P = 0.020), lymphatic metastasis (P = 0.005) and high Ki-67 LI (P < 0.001). NOK positive NSCLC patients had a significantly shorter survival time (P = 0.004, Log-rank test) and the prognostic significance of NOK expression was apparent in squamous cell carcinoma patients (P = 0.022). Multivariate analysis indicated that NOK expression may be an independent prognostic factor in NSCLC (hazard ratio [HR], 1.731; P = 0.043). Conclusions: Our results indicate that NOK expression is of clinical significance and can serve as a prognostic biomarker in NSCLC.