Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma

Wang, Shanshan; Jiang, Wei; Chen, Xiangmei; Zhang, Chao; Li, Hui; Hou, Weimin; Liu, Zhongmin; McNutt, Michael A.; Lu, Fengmin; Li, Gang

doi:10.1016/j.jhep.2012.03.029

Cited by 59 publications

(44 citation statements)

References 23 publications

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“…Multivariate analyses revealed that the Fn14 expression was an independent risk factor affecting recurrence and survival after curative resection, with the highest HR value for recurrence (HR 1.541, 95% CI 1.187-2.002; P=0.001) and the third highest value for survival (HR 1.398, 95% CI 1.090-1.793; P=0.008). Our data also showed, that high Fn14 expression in HCC tumors correlated with higher serum AFP levels, which might be explained by a RAR-AFP interaction and binding to the regulatory DNA region of the Fn14 gene in neoplastic tissues of HCC patients (Wang et al, 2012). HCC patients with various PVTT types had different prognoses.…”

Section: Discussionsupporting

confidence: 65%

Roles of Fibroblast Growth Factor-inducible 14 in Hepatocellular Carcinoma

Hu²,

Shi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson χ 2 test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy.

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Section: Discussionsupporting

confidence: 65%

Roles of Fibroblast Growth Factor-inducible 14 in Hepatocellular Carcinoma

Hu²,

Shi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Hepatic Fn14 expression is also upregulated in other experimental liver injuries, such as that induced by CCl 4 , a 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet, acetaminophen, and choline-deficient, ethionine-supplemented diets (1,30). Moreover, induction of Fn14 expression is observed in chronic human liver diseases, including nonalcoholic steatohepatitis, alcoholic liver disease, chronic hepatitis C (12), and hepatocellular carcinoma (8,32).…”

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confidence: 99%

Role of Fn14 in acute alcoholic steatohepatitis in mice

Karaca

Xie

Moylan

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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TNF-like weak inducer of apoptosis (TWEAK) is a growth factor for bipotent liver progenitors that express its receptor, fibroblast growth factor-inducible 14 (Fn14), a TNF receptor superfamily member. Accumulation of Fn14(+) progenitors occurs in severe acute alcoholic steatohepatitis (ASH) and correlates with acute mortality. In patients with severe ASH, inhibition of TNF-α increases acute mortality. The aim of this study was to determine whether deletion of Fn14 improves the outcome of liver injury in alcohol-consuming mice. Wild-type (WT) and Fn14 knockout (KO) mice were fed control high-fat Lieber deCarli diet or high-fat Lieber deCarli diet with 2% alcohol (ETOH) and injected intraperitoneally with CCl₄ for 2 wk to induce liver injury. Mice were euthanized 3 or 10 days after CCl₄ treatment. Survival was assessed. Liver tissues were analyzed for cell death, inflammation, proliferation, progenitor accumulation, and fibrosis by quantitative RT-PCR, immunoblot, hydroxyproline content, and quantitative immunohistochemistry. During liver injury, Fn14 expression, apoptosis, inflammation, hepatocyte replication, progenitor and myofibroblast accumulation, and fibrosis increased in WT mice fed either diet. Mice fed either diet expressed similar TWEAK/Fn14 levels, but ETOH-fed mice had higher TNF-α expression. The ETOH-fed group developed more apoptosis, inflammation, fibrosis, and regenerative responses. Fn14 deletion did not reduce hepatic TNF-α expression but improved all injury parameters in mice fed the control diet. In ETOH-fed mice, Fn14 deletion inhibited TNF-α induction and increased acute mortality, despite improvement in liver injury. Fn14 mediates wound-healing responses that are necessary to survive acute liver injury during alcohol exposure.

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“…Liver retains the potential to repair itself in response to injury. We therefore analysed the expression of α-fetoprotein associated with cell proliferation although the precise mechanism of its function is not known (Wang S1 et al 2012). We examined if SULF1/SULF2 expression is related to liver regeneration in samples with fatty liver degeneration, chronic hepatitis and cirrhosis using normal adult and HCC tumour tissues as negative and positive controls ( Figure 5).…”

Section: Resultsmentioning

confidence: 99%