Abstract
BackgroundHepatocellular carcinoma (HCC) is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions.Methods and FindingsWe characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption). Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy.ConclusionOur study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis.
Highlights
Hepatocellular carcinoma (HCC) represents an endemic burden worldwide, partially due to delayed diagnosis and multiple risk factors that contribute to a permanent high incidence [1,2]
Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis
We studied a series of human HCC samples for DNA promoter methylation using Illumina bead array analysis of 1505 CpG sites in 807 cancer-related gene promoters
Summary
Hepatocellular carcinoma (HCC) represents an endemic burden worldwide, partially due to delayed diagnosis and multiple risk factors that contribute to a permanent high incidence [1,2]. Well-known risk factors include chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, toxic, metabolic and immune-related conditions [3] In all these conditions, the development of malignancy is the consequence of a multistep process, including several morphologically recognizable stages and usually associated with a context of cirrhosis, a precancerous condition combining increased proliferation and prolonged environmental stress. Somatic mutations in several tumor suppressor genes (such as TP53, p16, and RB), oncogenes (including c-MYC and b-catenin), and other cancer-associated genes (including E-cadherin and cyclin D1) have been observed in HCC. These changes have been detected mainly in late stages of HCC development [4]. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
