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

被引:49
作者
Cai, Shao-hang [2 ,3 ]
Lu, Shi-xun [2 ,3 ]
Liu, Li-li [2 ,3 ]
Zhang, Chris Zhiyi [2 ,3 ]
Yun, Jing-ping [1 ]
机构
[1] Sun Yat Sen Univ, Dept Pathol, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China,Canc Ctr, 651 Dongfeng East Rd, Guangzhou 510060, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Canc Ctr, Dept Pathol, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
hepatocyte nuclear factor 4 alpha; promoter; 1; 2; hepatocellular carcinoma; prognostic biomarker; P1; PROMOTER; VISCERAL ENDODERM; GENE-EXPRESSION; HNF4-ALPHA; ISOFORMS; LIVER; FACTOR-4-ALPHA; DIFFERENTIATION; GASTRULATION; REQUIRES;
D O I
10.1177/1756283X17725998
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Hepatocyte nuclear factor 4 alpha (HNF4 alpha) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4 alpha transcribed by promoter 1 (P1-HNF4 alpha) 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 alpha transcribed by promoter 2 (P2-HNF4 alpha) 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 alpha and clinical features of HCC patients were analysed. Kaplan-Meier analysis was conducted to assess the prognostic value of P2-HNF4 alpha. Results: The results showed that the expression of P2-HNF4 alpha in HCC was noticeably increased in HCC tissues compared with the nontumourous tissues. In addition, P1-HNF4 alpha expression was negatively correlated with P2-HNF4 alpha expression (p=0.023). High P2-HNF4 alpha 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 alpha 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 alpha in cancer development needs to be further refined. P2-HNF4 alpha, different from P1-HNF4 alpha, 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.
引用
收藏
页码:761 / 771
页数:11
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