Potential biomarkers involving IKK/RelA signal in early stage non-small cell lung cancer

Abstract

The clinical relevance of nuclear factor κB (NF-κB) and its regulatory molecules on prognosis of patient with early stages of non-small cell lung cancer (NSCLC), remains unclear. Therefore, we conducted biomarker analyses with survival in patients with stages I and II NSCLC. Tumor samples were collected from 88 patients with early-stage NSCLC (stages I, II). A minimum follow-up period of 5 years was required. RelA, phosphorylated IκB (pIκBα), pIKKα/β were detected by immunostaining. NF-κB DNA binding activity was assessed by electrophoretic mobility shift assay. Association of clinical and pathologic variables (e.g. sex, age, pathologic stage) with relevant molecules was determined by Pearson's χ2 test or Fisher's exact test. Survival analysis based on single expression of RelA, pIκBα, pIKKα/β as well as composite expressions were evaluated using Cox proportional hazards regression models, and log rank test followed Kaplan-Meier estimates. RelA, pIκBα, pIKKα/β were observed as increased expression in NSCLC tissues compared with adjacent normal tissues and normal lung tissues. These molecules were associated with tumor-node-metastasis stages, T stages and histological status, respectively. Among the molecules analyzed, RelA and pIκBα-positive were statistically significant predictors of patient death in the entire patient population adjusted by age, gender and smoking status; furthermore both RelA and pIκBα-positive was the strongest prognostic indicators of poor prognosis by univariate and multivariate analyses. Borderline positive correlations were observed between RelA and pIκBα or pIKKα/β expression. In this cohort of early-stage NSCLC patients, molecular markers, especially composite application of multiple biomarkers (both nuclear RelA and cytoplasmic pIκB-α expression) that independently predict overall survival have been identified. © 2008 Japanese Cancer Association.