Combined Prognostic Value of Both RelA and IκB-α Expression in Human Non–Small Cell Lung Cancer

Abstract

We sought to investigate the prognostic significance of nuclear factor (NF)-kappaB activity, especially nuclear RelA and IkappaB-alpha expression patterns, in non-small cell lung cancer (NSCLC). A total of 116 patients with pathologically confirmed stage I to II NSCLC were included. Immunohistochemical analysis and electrophoretic mobility shift assays of NF-kappaB were performed to determine RelA and phosphorylated IkappaB-alpha staining, and DNA binding activity of NF-kappaB in human NSCLC. Downstream genes, including VEGF and IL-8, were also assessed. The prognostic significance of a single expression of RelA, phosphorylated IkappaB-alpha, and b-composite expressions was evaluated by Cox proportional hazard regression models and by Kaplan-Meier survival analyses. Correlation between RelA/IkappaB-alpha expression status and clinicopathological features of NSCLC was also analyzed. NF-kappaB DNA binding activity, VEGF, and IL-8 showed correlation with nuclear RelA and cytoplasmic pIkappaB-alpha expression. Expression of nuclear RelA/NF-kappaB showed an increase in NSCLC tissue compared with adjacent normal tissue and normal lung tissue. There was a positive correlation between NF-kappaB activation (nuclear translocation of RelA) and tumor clinicopathological features such as tumor grade, including T stages, N stages, and tumor, node, metastasis system stages, smoking status, and age. Positive correlation was observed between nuclear RelA and cytoplasmic pIkappaB-alpha. Both nuclear RelA and cytoplasmic pIkappaB-alpha were associated with poor prognosis by univariate and multivariate analyses. Nuclear RelA and cytoplasmic pIkappaB-alpha expression are associated with a poorer prognosis in NSCLC patients. In particular, composite application of these two biomarkers might be of greater value than application of a single marker to identify patients at high risk, even at an early clinical stage.