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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

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

Cai Shao-Hang SH Lu Shi-Xun SX Liu Li-Li LL Zhang Chris Zhiyi CZ Yun Jing-Ping JP

Therapeutic advances in gastroenterology 20170825 10

<h4>Background</h4>Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear.<h4>Methods</h4>A total of 615 HCC specimens were obtained to construct tissue microarr ...[more]

PMID: 29051787

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Project description:Objective:Hepatocellular carcinoma (HCC) is a disease that is associated with high mortality; currently, there is no curative and reliable treatment. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) is the key signaling molecule in the wingless and INT-1/planar cell polarity (WNT/PCP) pathway. This study aimed to elucidate the prognostic significance of CELSR3 in HCC patients. Methods:The Cancer Genome Atlas (TCGA) database, the Cancer Cell Line Encyclopedia (CCLE) database and the Gene Expression Omnibus (GEO) database were used to analyze the expression of CELSR3 mRNA in HCC samples and cells. The relationship between CELSR3 mRNA and clinical features was assessed by the chi-square test. the diagnostic and predictive value of CELSR3 mRNA expression were analyzed using the receiver operating characteristic (ROC) curve. Kaplan-Meier curve and Cox regression analyses were performed to assess the prognostic value of CELSR3 mRNA in HCC patients. Finally, all three cohorts database was used for gene set enrichment analysis(GSEA) and the identification of CELSR3-related signal transduction pathways. Results:The expression of CELSR3 mRNA was upregulated in HCC, and its expression was correlated with age (P = 0.025), tumor status (P = 0.022), clinical stage (P = 0.003), T classification (P = 0.010), vital status (P = 0.001), and relapse (P = 0.005). The ROC curve assessment indicated that CELSR3 mRNA expression has high diagnostic value in HCC and in the subgroup analysis of stage. In addition, the Kaplan-Meier curve and Cox analyses suggested that patients with high CELSR3 mRNA expression have a poor prognosis, indicating that CELSR3 mRNA is an independent prognostic factor for the overall survival of HCC patients. GSEA showed that GO somatic diversification of immune receptors, GO endonuclease activity, GO DNA repair complex and GO somatic cell DNA recombination, were differentially enriched in the meta-GEO cohort, the HCC cell line cohort and the TCGA cohort of the high CELSR3 mRNA expression phenotype. Conclusion:Our results indicate that CELSR3 mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients.

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

Publications

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

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