Hepatocellular carcinoma: Towards personalized medicine

Miki, Daiki; Ochi, Hidenori; Hayes, C. Nelson; Aikata, Hiroshi; Chayama, Kazuaki

doi:10.1111/j.1349-7006.2012.02242.x

Cited by 46 publications

(26 citation statements)

References 84 publications

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“…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)(6)(7)(8). Progress has been made in identifying molecular markers for the initiation and progression of HCC that will likely increase the rate of early and potentially life-saving diagnoses (9)(10)(11)(12). The expanding amount of knowledge regarding the molecular foundations of HCC makes it increasingly clear that successful therapy requires treatment tailored to the individual patient (8).…”

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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Section: Introductionmentioning

confidence: 99%

NRAGE promotes the malignant phenotype of hepatocellular carcinoma

et al. 2016

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“…In Taiwan, universal HBV vaccination has almost eradicated HBV-related pediatric liver cancer (209). Currently, there is no vaccine available for HCV, and interferon treatment is effective in clearing acute HCV infections in only about onethird of patients (210). Hence, screening and treatment for HCV infection in high-risk populations such as intravenous drug users, among whom the prevalence of HCV infection is about 90%, is an important strategy for the prevention of HCV-mediated HCC (171).…”

Section: Hepatitis Virus Detection Prevention and Treatmentmentioning

confidence: 99%

Multiple Infections and Cancer: Implications in Epidemiology

Vedham

Divi

Starks

et al. 2014

Technol Cancer Res Treat

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Approximately 18% of the global cancer burden has been attributed to infectious agents, with estimates ranging from 7% in developed countries to about 22% in developing countries.Chronic infections caused by the hepatitis B and C viruses, human papilloma viruses (HPV), and Helicobacter pylori (H. pylori) are reported to be responsible for approximately 15% of all human cancers. Interestingly, although many of the infectious agents that have been associated with cancer-such as HPV, Epstein-Barr virus (EBV), and H. pylori-are highly prevalent in the world, most infected individuals do not develop cancer but remain lifelong carriers. Malignancies associated with infectious agents may result from prolonged latency as a result of chronic infections. Pathogenic infections are necessary but are not sufficient for cancer initiation or progression. Cancer initiation may require additional cofactors, including secondary infections. Therefore, in patients with chronic infection with one agent, secondary co-infection with another agent may serve as an important co-factor that may cause cancer initiation and progression. Additionally, opportunistic co-infections could significantly inhibit response to cancer treatment and increase cancer mortality. Co-infections are relatively common in areas with a high prevalence of infectious agents, especially in developing countries. These co-infections can cause an imbalance in the host immune system by affecting persistence of and susceptibility to malignant infections. Several articles have been published that focus on infectious agents and cancer. In this article, we discuss the role of infectious agents in malignancies, highlight the role of multiple/co-infections in cancer etiology, and review implications for cancer epidemiology.

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“…Eastern Asian countries such as Japan and China are areas where HCC is highly prevalent due to serious hepatitis C virus (HCV)/ hepatitis B virus (HBV) infection in the population (1,2). Therapeutic regimens including liver transplantation, surgical resection, and local-regional therapy such as transarterial chemoembolization (TACE) play a major role in HCC management.…”

Section: Introductionmentioning

confidence: 99%