Expression of nuclear factor-kappaB and its clinical significance in nonsmall-cell lung cancer

Abstract

Background: It has been known that transcription factor nuclear factor (NF)-kappaB plays an important role in cell proliferation and oncogenesis. The aims of this study were to evaluate expression levels of NF-kappaB in nonsmall-cell lung cancer (NSCLC) and to elucidate its clinical significance and prognostic value for patients with NSCLC.

Methods: Using 45 tumor tissue specimens from 45 patients with NSCLC who underwent surgery, we investigated the expression of NF-kappaB using Western blotting analysis. Apoptotic rate of NSCLC cells with different expression of NF-kappaB was determined by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling) assay. Paraffin-embedded tissue blocks from 71 consecutive patients with NSCLC were obtained for immunohistochemical staining.

Results: The expression level of NF-kappaB in poorly or moderately differentiated lung cancer cells was higher than that in well-differentiated ones (p = 0.001). The apoptotic rate was lower for lung cancer cells with higher NF-kappaB expression than for those with lower NF-kappaB expression (p = 0.0238). Furthermore, expression of NF-kappaB was correlated with caspase-3, cyclooxygenase-2, and p53 expression in lung cancer cells that were examined. Most NSCLC cells showed nuclear staining pattern and the nuclear positive rate was 67.6% (48 of 71 specimens). Immunohistochemical NF-kappaB expression in patients with NSCLC was an independent prognostic factor for overall survival.

Conclusions: The results of this study suggest that expression of NF-kappaB may correlate with lung cancer differentiation. Overexpression of NF-kappaB inhibits tumor cell apoptosis and indicates an unfavorable prognosis for overall survival in some patients with NSCLC.