Expression of dual-specificity tyrosine-(Y)-phosphorylation–regulated kinase 2 (DYRK2) can be a favorable prognostic marker in pulmonary adenocarcinoma

Abstract

We investigated the possibility of DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase gene, to predict survival for patients with pulmonary adenocarcinoma. One hundred forty-four patients with pulmonary adenocarcinoma underwent surgery in our institute from 2000 to 2008. We used immunohistochemical analysis and real-time reverse-transcriptase polymerase chain reaction to determine the expression of DYRK2 and compared this with the clinicopathologic factors and survival. We found no correlation between DYRK2 expression by immunohistochemical and clinicopathologic factors; however, a negative nodal status and negative lymphatic invasion were significantly associated with DYRK2 expression by reverse-transcriptase polymerase chain reaction. Five-year disease-free survival in the DYRK2-positive group (75.4%) was significantly different from that in the negative group (55.4%; P = .03) by immunohistochemical analysis. The 5-year overall survival of 89.2% in the DYRK2-positive group was better than the 66.3% survival of the DYRK2-negative group (P = .01). Quantitative real-time reverse-transcriptase polymerase chain reaction analyses showed a significant difference between positive and negative expressions for disease-free survival (P = .003) and overall survival (P = .007). In multivariate Cox regression analysis, negative DYRK2 protein and messenger RNA expression showed a worse prognostic value of survival (hazard ratio [HR] = 4.7, 95% confidence intervals [CI] = 1.5-14.5, P=.007; HR = 2.5, 95% CI = 1.1-6.1, P = .04, respectively). When we analyzed adenocarcinoma cases except for bronchioloalveolar carcinoma, we found a close correlation between DYRK2 expression by immunohistochemical analysis and nodal status (P = .03). Furthermore, disease-free survivals between positive and negative groups of DYRK2 expression by immunohistochemistry (P = .03) and reverse-transcriptase polymerase chain reaction (P = .02) without bronchioloalveolar carcinoma were significantly different. Overall survivals in both groups showed significant differences by immunohistochemistry (P = .02) but not by reverse-transcriptase polymerase chain reaction (P = .08). These data showed that DYRK2 expression is associated with a favorable prognosis.