DNA methylation: potential biomarker in Hepatocellular Carcinoma
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DNA methylation: potential biomarker in Hepatocellular Carcinoma Way-Champ Mah1,2,3 and Caroline GL Lee1,2,3,4*
Abstract 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. Keywords: Epigenetics, Methylation, Biomarker, CIMP, Hepatocellular carcinoma, Prognosis, Diagnosis
Introduction Hepatocellular Carcinoma (HCC) is one of the most frequent cancers in the world and annually, about 600,000 patients died of liver cancer [1]. This disease is often associated with poor prognosis because patients are either diagnosed at very late stage or experienced recurrence after resection [2]. In fact, more than half of HCC patients died within 12 months post diagnosis, and less than 6% of them have an average survival rate of 5 years [3]. Liver transplantation and resection are the only two curative therapies available; however, in order to qualify for such therapies, patients need to be diagnosed early with HCC [4]. Presently, serum alpha-fetoprotein (AFP) concentration and hepatic ultrasonography are used in * Correspondence: [email protected] 1 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore 2 Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Level 6, Lab 5, 11 Hospital Drive, Singapore 169610, Singapore Full list of author information is available at the end of the article
HCC surveillance program, where high risk patients are screened for HCC in every six months [5]. As for actual diagnosis,
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