NF-κB Expression and Outcomes in Solid Tumors: A Systematic Review and Meta-Analysis.

Abstract

Nuclear factor-kappaB (NF-κB) is a key inflammatory transcription factor expressed frequently in tumors. Numerous studies have investigated the correlation between NF-κB expression and prognosis in solid tumors, but the conclusions are still in contradiction. Here, we conduct a meta-analysis to explore the overall association of NF-κB overexpression and survival in human solid tumors. Pubmed and EBSCO databases were searched for studies evaluating expression of NF-κB (as measured by immunohistochemistry) and overall survival (OS) and disease-free survival (DFS) in solid tumors. Published data were extracted and computed into odds ratios (ORs) for death at 3, 5, and 10 years. Data were pooled using the Mantel-Haenszel random-effect model. All statistical tests were two-sided. Forty-four studies with a total of 4418 patients were included in this meta-analysis. NF-κB overexpression was associated with worse OS at 3 years (OR = 3.40, 95% confidence interval [CI] = 2.41-4.79, P < 0.00001), 5 years (OR = 2.72, 95% CI = 1.92-3.85, P < 0.00001), and 10 years (OR = 2.63, 95% CI = .34-5.16, P = 0.005) of solid tumors. Results for 3- and 5-year DFS were similar. NF-κB expression was associated with poor 3-year OS in both Tumor, Lymph Node, Metastasis stage I-II (OR = 9.11, 95% CI = 2.90-28.68, P = 0.0002) and III-IV (OR = 2.59, 95% CI = 1.61-4.15, P < 0.0001). There is no correlation between cellular localization of NF-kB overexpression and OS of solid tumors. Among the tumor types, NF-κB was associated with worse 3 year-OS of colorectal cancer (OR = 2.70, 95% CI = 1.64-4.46, P < 0.0001), esophageal carcinoma (OR = 6.00, 95% CI = 3.29-10.94, P < 0.0001) and worse 5 year-OS of colorectal cancer (OR = 2.72, 95% CI = 1.92-3.85, P < 0.00001), esophageal carcinoma (OR = 5.96, 95% CI = 3.48-10.18, P = 0.03), and nonsmall cell lung cancer (OR = 1.69, 95% CI = 1.20-2.38, P = 0.002). Expression of NF-κB is associated with worse survival in most solid tumors irrespective of NF-κB localization.