Combined prognostic value of both RelA and IkappaB-alpha expression in human non-small cell lung cancer.
BACKGROUND
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).


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-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.


RESULTS
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.


CONCLUSIONS
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.
Zhang
Dianliang
D
Department of Surgery, Affiliated Hospital of Qingdao University, Qingdao, PR China.
Jin
Xianqing
X
Wang
Fuling
F
Wang
Shan
S
Deng
Chun
C
Gao
Zongwei
Z
Guo
Chunbao
C
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D051996:Transcription Factor RelA / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D051996:Transcription Factor RelA; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072000:NF-KappaB Inhibitor alpha