Overexpression of jun activation domain‐binding protein 1 in nonsmall cell lung cancer and its significance in p27 expression and clinical features

Abstract

Decreased expression of p27, which is an inhibitor of cyclin-dependent kinase, is associated with cancer aggressiveness. It is believed that Jun activation domain-binding protein 1 (Jab1) plays a role in p27 degradation in a manner that is independent from the role played by S-phase kinase-associated protein 2 (Skp2). To examine the clinical significance of Jab1 in nonsmall cell lung cancer (NSCLC), the protein expression of Jab1 in tumor tissues was investigated with regard to the expression of p27 and Skp2. The clinicopathologic features and immunohistochemical expression levels of Jab1, p27, and Skp2 proteins were studied in 138 specimens from patients who underwent surgical resection for NSCLC. Survival analyses were performed by using the Kaplan-Meier method and Cox regression models. High Jab1 expression (>50% of cancer cell nuclei stained) was observed in 81 specimens (59%). In Skp2-negative specimens (n = 81), an inverse correlation between the protein expression of p27 and Jab1 was observed both with the chi-square test (P = .02) and with the Mann-Whitney U test (P = .02). High Jab1 expression levels were related to poor outcomes in 118 patients who underwent complete resection, with a 5-year overall survival rate of 43.9% for patients who had high Jab1 expression and 63.1% for patients who had low Jab1 expression (P = .01). This difference was greater in patients who had Skp2-negative specimens (51.9% vs. 79.3% (P = .02), but it was not significant in patients who had Skp2-positive specimens. The multivariate analysis revealed that Jab1 expression was an independent prognostic factor for survival in patients with NSCLC (relative risk, 2.247; P = .01). The current results showed for the first time that high Jab1 protein expression is related to poor outcome in patients with NSCLC and that this protein may be a target of therapy in NSCLC.