NEMO expression in human hepatocellular carcinoma and its association with clinical outcome

Abstract

The nuclear factor κ-light-chain enhancer of activated B-cells (NF-κB) signaling pathway is regarded as an important factor in inflammation and carcinogenesis. Recently, a role in hepatocarcinogenesis has been attributed to the NF-κB regulatory subunit IKKγ (NEMO) using knockout mice. However, a detailed investigation of NEMO expression in human hepatocellular carcinomas (HCCs) has not yet been reported. We selected 85 HCC patients who had undergone curative liver resection and analyzed NEMO expression of the respective tumors by immunohistochemistry, Western blotting, and real-time PCR. NEMO expression was correlated with clinicopathological parameters, and the impact on 5-year disease-free survival and 5-year overall survival was calculated using multivariate Cox proportional models. In our study, complete loss of NEMO immunoreactivity was found in 34 (40%) of 85 HCCs compared with their adjacent nonneoplastic tissue (P < .05). NEMO messenger RNA (mRNA) expression was detected in all HCC cases; however, no correlation between NEMO immunoreactivity and mRNA level was found. Five-year overall survival rates for patients with low and high NEMO expression were 22% and 50%, respectively (P = .049). However, high tumor stage, but not level of NEMO expression, was confirmed as an independent poor prognostic factor for 5-year disease-free survival (hazards ratio [HR] = 2.1, 95% confidence interval [CI] = 1.3-3.6, P = .009) and 5-year overall survival (HR = 2.5, CI = 1.4-4.4, P = .002). In conclusion, a loss of NEMO immunoreactivity occurs in a substantial proportion of human HCCs. Although low NEMO expression is correlated with a poor 5-year overall survival in patients with HCC, NEMO cannot be regarded as an independent prognostic marker for predicting the clinical outcome of patients suffering from HCC.