Evaluation of MAGE‐D4 expression in hepatocellular carcinoma in Japanese patients

“…The MAGE-I subgroup consists of products yielded by numerous X chromosome clustered genes, including MAGE-A, -B and -C, which are typically expressed in cancer cells of various origins, but not in adult tissues, with the exception of germ-line cells in the placenta, ovaries and testes (15,16). By contrast, the MAGE-II subgroup, including MAGE-D variants, do not have defined chromosome clustering and are cancer non-specific, with near universal expression in normal adult tissues and germ-line cells (14,16,17).…”

Section: Introductionmentioning

confidence: 99%

“…MAGE proteins, as tumor-associated antigens, have attracted increasing attention regarding the development of vaccine-based immunotherapy for the treatment of cancer (18). Our strategy for addressing this issue involves detailed analysis of the literature to identify potential markers and targets for therapy of HCC (15). For example, a previous meta-analysis indicated that glypican-3, des-γ-carboxyprothrombin, α-L-fucosidase and vascular endothelial growth factor may serve as suitable serological markers for HCC (19).…”

Section: Introductionmentioning

confidence: 99%

NRAGE promotes the malignant phenotype of hepatocellular carcinoma

et al. 2016

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Abstract. Hepatocellular carcinoma (HCC) is a fatal disease, primarily due to the limited effective therapies available for patients with advanced or recurrent stages of the disease. Therefore, in order to improve patient prognosis, it is important to identify an informative biomarker for HCC progression, as well as a molecular target for therapy. Neurotrophin receptor-interacting melanoma antigen-encoding protein (NRAGE), a member of the type II melanoma-associated antigen family, mediates apoptosis and cell death through interactions with a wide range of proteins, and is implicated as a tumor suppressor or oncoprotein depending on cell type. However, the role of NRAGE in HCC is currently unknown, therefore, the present study aimed to identify the underlying function of NRAGE in HCC tumorigenesis. Resected tumor and non-cancerous liver tissues from 151 patients with HCC, alongside HCC cell lines, were analyzed by polymerase chain reaction and immunohistochemical techniques to determine NRAGE expression levels, as well as the expression levels of potential genes encoding interacting proteins. It was demonstrated that the expression levels of NRAGE mRNA correlated significantly with those of apoptosis-antagonizing transcription factor (AATF), and were not affected by cirrhosis in non-cancerous liver tissues when compared to elevated levels in HCC tissues. The expression patterns of NRAGE protein and mRNA were consistent among 30 representative specimen pairs. Furthermore, increased NRAGE expression in patients with HCC correlated significantly with a shorter disease-specific survival time, and was identified as an independent prognostic factor via multivariate analysis (hazard ratio, 2.23; 95% confidence interval, 1.06-3.83; P=0.020). Therefore, the results of the present study indicated that increased NRAGE expression affects HCC progression via its interaction with AATF, and may represent a novel biomarker and molecular target for the treatment of HCC. IntroductionHepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors, with high rates of mortality and morbidity (1,2). The worldwide incidence of HCC is ~1,000,000 cases per year and is equivalent to its mortality rate (3). Furthermore, HCC ranks as the third highest cause of cancer-associated mortality (4). Such statistics are largely explained by the difficulties faced when diagnosing HCC, with diagnosis often only confirmed once the disease is at a late stage and palliative care is the only treatment option available. An important strategy to improve patient outcome involves the identification of disease risk factors and the maintenance of vigilant surveillance of high-risk individuals to allow for recognition of the disease at a stage that is responsive to treatment with curative intent. Therefore, it is fundamental that high-risk groups are identified, followed by successful implementation of a surveillance program and recall protocol following any abnormal findings (5-8). Progress has been made in identifying molecular markers for the i...

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“…We purchased nine HCC cell lines from the American Type Culture Collection (Manassas, VA, usA) and cultured cells as previously described (23). Primary HCC and adjacent liver tissues were collected from 144 patients who underwent hepatectomy for HCC at Nagoya university Hospital between january 1998 and january 2012.…”

Section: Methodsmentioning

confidence: 99%

Translational implication of Kallmann syndrome-1 gene expression in hepatocellular carcinoma

Tanaka

Kanda

Sugimoto

et al. 2015

International Journal of Oncology

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Abstract. Accumulation of epigenetic alterations causes inactivation of tumor suppressors and contributes to the initiation and progression of hepatocellular carcinoma (HCC).Identification of methylated genes is necessary to improve our understanding of the pathogenesis of HCC and develop novel biomarkers and therapeutic targets. The Kallmann syndrome-1 (KAL1) gene encodes an extracellular matrixrelated protein with diverse oncological functions. However, the function of KAL1 in HCC has not been examined. We investigated the methylation status of the KAL1 promoter region in HCC cell lines, and evaluated KAL1 mRNA levels and those of genes encoding potential interacting cell adhesion factors. KAL1 mRNA expression level was heterogeneous in nine HCC cell lines, and reactivation of KAL1 mRNA expression was observed in cells with promoter hypermethylation of KAL1 gene after demethylation. In addition, KAL1 mRNA levels inversely correlated with those of ezrin in all nine HCC cell lines. KAL1 expression levels in 144 pairs of surgically-resected tissues were determined and correlated to clinicopathological parameters. KAL1 mRNA level was independent of the background liver status, whereas HCC tissues showed significantly lower KAL1 mRNA levels than corresponding noncancerous liver tissues. Downregulation of KAL1 mRNA in HCC was significantly associated with malignant phenotype characteristics, including elevated tumor markers, larger tumor size, vascular invasion, and hypermethylation of KAL1. Patients with downregulation of KAL1 were more likely to have a shorter overall survival than other patients, and multivariate analysis identified downregulation of KAL1 as an independent prognostic factor (hazard ratio 2.04, 95% confidence interval 1.11-3.90, P=0.022). Our results indicated that KAL1 may act as a putative tumor suppressor in HCC and is inactivated by promoter hypermethylation. KAL1 may serve as a biomarker of malignant phenotype of HCC.

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Evaluation of MAGE‐D4 expression in hepatocellular carcinoma in Japanese patients

Abstract: Overexpression of MAGE-D4 may be a predictive marker of early recurrence and mortality in patients with HCC.

Cited by 21 publications

References 33 publications

Reduced Expression of Adherens Junctions Associated Protein 1 Predicts Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy

Reduced Expression of Adherens Junctions Associated Protein 1 Predicts Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy

NRAGE promotes the malignant phenotype of hepatocellular carcinoma

Translational implication of Kallmann syndrome-1 gene expression in hepatocellular carcinoma

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