Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma.

ABSTRACT: BACKGROUND:Hepatocyte nuclear factor 4 alpha (HNF4?) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4? transcribed by promoter 1 (P1-HNF4?) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4? transcribed by promoter 2 (P2-HNF4?) in HCC remains unclear. METHODS:A total of 615 HCC specimens were obtained to construct tissue microarrays and perform immunohistochemistry. The relationship between P2-HNF4? and clinical features of HCC patients were analysed. Kaplan-Meier analysis was conducted to assess the prognostic value of P2-HNF4?. RESULTS:The results showed that the expression of P2-HNF4? in HCC was noticeably increased in HCC tissues compared with the nontumourous tissues. In addition, P1-HNF4? expression was negatively correlated with P2-HNF4? expression (p?=?0.023). High P2-HNF4? expression was significantly associated with poor differentiation of HCC (p = 0.002) and vascular invasion (p =?0.017). Kaplan-Meier analysis showed that P2-HNF4? expression was closely correlated with overall survival in the training group (p = 0.01), validation group (p =?0.034), and overall group of patients with HCC (p < 0.001). CONCLUSIONS:Our data show that the role of HNF4? in cancer development needs to be further refined. P2-HNF4?, different from P1-HNF4?, is markedly upregulated and serves as an oncogene-associated protein in HCC. Our study therefore provides a promising biomarker for prognostic prediction and a potential therapeutic target for HCC.

SUBMITTER: Cai SH 

PROVIDER: S-EPMC5638181 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature