Methylation of serum insulin‐like growth factor‐binding protein 7 promoter in hepatitis B virus‐associated hepatocellular carcinoma

Li, Feng; Fan, Yu–Chen; Gao, Shuai; Sun, Feifei; Yang, Yang; Wang, Kai

doi:10.1002/gcc.22120

Cited by 33 publications

(34 citation statements)

References 30 publications

(41 reference statements)

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“…Lastly, Li et al discovered that in HBV-associated HCC, IGFBP7 was more methylated compared to chronic hepatitis B patients and normal controls. Also, its methylation status was associated with vascular invasion in HCC [115]. …”

Section: Reviewmentioning

confidence: 99%

DNA methylation: potential biomarker in Hepatocellular Carcinoma

Mah

Lee

2014

Biomark Res

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Hepatocellular Carcinoma (HCC) is one of the most common cancers in the world and it is often associated with poor prognosis. Liver transplantation and resection are two currently available curative therapies. However, most patients cannot be treated with such therapies due to late diagnosis. This underscores the urgent need to identify potential markers that ensure early diagnosis of HCC. As more evidences are suggesting that epigenetic changes contribute hepatocarcinogenesis, DNA methylation was poised as one promising biomarker. Indeed, genome wide profiling reveals that aberrant methylation is frequent event in HCC. Many studies showed that differentially methylated genes and CpG island methylator phenotype (CIMP) status in HCC were associated with clinicopathological data. Some commonly studied hypermethylated genes include p16, SOCS1, GSTP1 and CDH1. In addition, studies have also revealed that methylation markers could be detected in patient blood samples and associated with poor prognosis of the disease. Undeniably, increasing number of methylation markers are being discovered through high throughput genome wide data in recent years. Proper and systematic validation of these candidate markers in prospective cohort is required so that their actual prognostication and surveillance value could be accurately determined. It is hope that in near future, methylation marker could be translate into clinical use, where patients at risk could be diagnosed early and that the progression of disease could be more correctly assessed.

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Section: Reviewmentioning

confidence: 99%

DNA methylation: potential biomarker in Hepatocellular Carcinoma

Mah

Lee

2014

Biomark Res

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“…The methylation silienced SOX11 expression might therefore result in the growth and invasion of tumor cells [30]. Second, tumor-derived mutant DNA in situ tissue might migrate into peripheral circulation and then lead to the detectable level of serum SOX11 promoter methylation [13,35].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, AFP could not be a satisfied biomarker for the early diagnosis of HCC [12]. Therefore, new effective biomarkers for the early detection of HCC are urgently needed [13].…”

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confidence: 99%

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Serum SOX11 promoter methylation is a novel biomarker for the diagnosis of Hepatitis B virus-related hepatocellular carcinoma

Teng¹,

Fan²,

Mu³

et al. 2016

neo

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Promoter methylation of tumor suppressor gene SOX11 has been reported to contribute to the diagnosis and prognosis of various cancerous diseases, including gastric cancer, hematopoietic malignancies and nasopharyngeal carcinoma. However, there is no data on the diagnostic potential of serum SOX11 promoter methylation in hepatocellular carcinoma (HCC). This study was therefore aimed to investigate the potential role of serum SOX11 promoter methylation as a noninvasive biomarker in the diagnosis of patients with hepatitis B virus (HBV) associated HCC. A total of 205 subjects were retrospectively included, which consisted of 111 HCC patients, 66 chronic hepatitis B (CHB) and 28 healthy controls (HCs). Methylation of SOX11 promoter was determined by methylation-specific polymerase chain reaction. The methylation frequency of serum SOX11 promoter in HCC patients (69.4%, 77/111) was significantly higher than that in CHB patients (13.6%, 9/66; χ2 = 51.467, P<0.001) and HCs (10.7%, 3/28; χ2 = 31.489, P<0.001). There was significant difference of serum SOX11 promoter methylation in HCC patients with vascular invasion (49/58) and those without vascular invasion (28/53; χ2 = 13.058, P<0.001). Furthermore, the sensitivity of 69% was identified for SOX11 methylation in discriminating HCC from CHB, which was significant higher than the sensitivity of 57% for serum alpha-fetoprotein (AFP) (P<0.05). Notably, SOX11 promoter methylation plus AFP showed a sensitivity of 85% in discriminating HCC from CHB. These results suggested that serum SOX11 promoter methylation might serve as a useful and noninvasive biomarker for the diagnosis of HCC.

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“…IGFBP7 functions as a tumor suppressor in a variety of cancers, including HCC, where its expression is markedly downregulated (7–9). Genomic deletion and promoter hypermethylation cause downregulation of IGFBP7 in HCC (7,10). Recombinant IGFBP7 (rIGFBP7) protein induces senescence and/or apoptosis and inhibits angiogenesis in diverse cancers either in vitro or in nude mice xenograft models (8,9,11).…”

Section: Introductionmentioning

confidence: 99%

IGFBP7 Deletion Promotes Hepatocellular Carcinoma

Akiel

Guo

et al. 2017

Cancer Research

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Activation of IGF signaling is a major oncogenic event in diverse cancers, including hepatocellular carcinoma (HCC). In this setting, the insulin-like growth factor binding protein IGFBP7 inhibits IGF signaling by binding the IGF-1 receptor (IGF-1R), functioning as a candidate tumor suppressor. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with pro-inflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects. Igfbp7 deletion increased proliferation and decreased senescence of hepatocytes and mouse embryonic fibroblasts, effects that were blocked by treatment with IGF-1 receptor inhibitor. Significant inhibition of genes regulating immune surveillance was observed in Igfbp7−/− murine livers, which was associated with a marked inhibition in antigen cross-presentation by Igfbp7−/− dendritic cells. Conversely, IGFBP7 overexpression inhibited growth of HCC cells in syngeneic immunocompetent mice. Depletion of CD4+ or CD8+ T lymphocytes abolished this growth inhibition, identifying it as an immune-mediated response. Our findings define an immune component of the pleiotropic mechanisms through which IGFBP7 suppresses HCC. Furthermore, they offer a genetically based preclinical proof of concept for IGFBP7 as a therapeutic target for immune management of HCC.

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Methylation of serum insulin‐like growth factor‐binding protein 7 promoter in hepatitis B virus‐associated hepatocellular carcinoma

Cited by 33 publications

References 30 publications

DNA methylation: potential biomarker in Hepatocellular Carcinoma

DNA methylation: potential biomarker in Hepatocellular Carcinoma

Serum SOX11 promoter methylation is a novel biomarker for the diagnosis of Hepatitis B virus-related hepatocellular carcinoma

IGFBP7 Deletion Promotes Hepatocellular Carcinoma

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