High RNF40 expression indicates poor prognosis of hepatocellular carcinoma.

Human RING-finger protein 40 (RNF40) is reported as an E3 ligase of H2B ubiquitination. RNF40 needs to couple with its homolog RNF20 to format a complex to regulate DNA double strand break (DSB) response and chromatin stability. Deficient expression of RNF40 might cause incorrect DNA repair and contribute to genomic instability, leading to an abnormal transcriptional program. Incorrect DSB repair and aberrant gene transcription play important roles in tumorigenesis. The role in primary hepatocellular carcinoma (HCC), however, remains unclear. In this study, we selected 103 cases of HCC for immunohistochemistry to explore the role of RNF40 in HCC. The relationship between RNF40 expression and clinicopathological features of HCC was evaluated. RNF40 was mainly localized in the nucleus, where the percentage of low and high staining of RNF40 in tumor tissues was 50.4% (53/103) and 49.6% (50/103), respectively. By contrast, in para-normal tissues the percentage was 92.2% (95/103) and 7.8% (8/103) respectively. Expression of RNF40 in tumor tissues was significantly higher than that in para-normal tissues (P>0.01). Expression of RNF40 had significant association with AFP and TNM tumor stage (both P>0.01). However, age, gender, Hepatitis B Virus infection, liver cirrhosis, tumor size, tumor number, differential stage, and tumor thrombosis were not associated with RNF40 expression. Meanwhile, HCC patients with high expression of RNF40 had lower 5 year overall survival rates and disease-free survival rates (P>0.05). RNF40 is, potentially, an independent prognostic factor for survival in HCC.