Expression of nuclear factor-kappaB and its clinical significance in nonsmall-cell lung cancer.
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.
Zhang
Zhenfa
Z
Department of Lung Cancer, Affiliated Cancer Hospital, Tian Jin Medical University, Tian Jin City, China.
Ma
Jianqun
J
Li
Ni
N
Sun
Nan
N
Wang
Changli
C
D000328:Adult; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002454:Cell Differentiation; D051546:Cyclooxygenase 2 / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020287:In Situ Nick-End Labeling; D015993:Life Tables; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D015854:Up-Regulation
D008565:Membrane Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases