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

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 = 1.34–5.16, 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.