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

¹ Department of Surgery, Affiliated Hospital of Qingdao University, Qingdao, P.R. China
² Laboratory of Surgery, Children’s Hospital of Chongqing Medical University, 22 Zhongshan Rd. Chongqing, 400014, Chongqing, P.R. China
³ Department of Chest Surgery, Linyi Municipal Hospital, Linyi, Shandong Province, P.R. China

Correspondence: Address correspondence and reprint requests to: Chunbao Guo, MD, PhD; E-mail: gchunbao{at}yahoo.com.cn

Background: We sought to investigate the prognostic significance of nuclear factor (NF)-B activity, especially nuclear RelA and IB- expression patterns, in non–small cell lung cancer (NSCLC).

Methods: A total of 116 patients with pathologically confirmed stage I to II NSCLC were included. Immunohistochemical analysis and electrophoretic mobility shift assays of NF-B were performed to determine RelA and phosphorylated IB- staining, and DNA binding activity of NF-B in human NSCLC. Downstream genes, including VEGF and IL-8, were also assessed. The prognostic significance of a single expression of RelA, phosphorylated IB-, and b-composite expressions was evaluated by Cox proportional hazard regression models and by Kaplan-Meier survival analyses. Correlation between RelA/IB- expression status and clinicopathological features of NSCLC was also analyzed.

Results: NF-B DNA binding activity, VEGF, and IL-8 showed correlation with nuclear RelA and cytoplasmic pIB- expression. Expression of nuclear RelA/NF-B showed an increase in NSCLC tissue compared with adjacent normal tissue and normal lung tissue. There was a positive correlation between NF-B 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 pIB-. Both nuclear RelA and cytoplasmic pIB- were associated with poor prognosis by univariate and multivariate analyses.

Conclusions: Nuclear RelA and cytoplasmic pIB- 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.

Key Words: Nuclear factor-B (NF-B) • Prognosis • Non–small cell lung cancer (NSCLC)