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Key drivers include epigenetic regulation, especially methylation-based control of gene expression. Methylation involves methylation-modifying proteins such as methyltransferases, associated binding proteins, and demethylases that coordinate methylation reading, binding, detection, and catalysis. These methylation processes influence tumor development, progression, invasion, cancer stem cell traits, tumor microenvironment and immune responses, chemotherapy resistance, and apoptosis. The review highlights methylation as a promising basis for early HCC detection and therapeutic targeting to improve drug resistance.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/research-progress-on-the-role-of-epigenetic-methylation-modification-in-hepatocellular-carcinoma-review/333467/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/research-progress-on-the-role-of-epigenetic-methylation-modification-in-hepatocellular-carcinoma-review/333467.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does epigenetic methylation play in hepatocellular carcinoma (HCC)?","Question",{"text":112,"@type":113},"Epigenetic methylation regulates gene expression without changing DNA sequence. Dysregulation of methylation in the epigenome is described as a driver in early HCC development and progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which methylation-modifying proteins are emphasized as key regulators?",{"text":117,"@type":113},"The review highlights proteins that modify methylation, including methyltransferases, their associated binding proteins, and demethylases. These regulators coordinate enzymes and binding partners to govern methylation sites.",{"name":119,"@type":110,"acceptedAnswer":120},"How does methylation contribute to HCC biomarkers and early detection?",{"text":121,"@type":113},"Aberrant methylation levels in HCC can occur in genes related to cell cycle, progression, and immune environment. The text also discusses non-invasive liquid biopsies using circulating tumor DNA and other methyl sequencing approaches to identify epigenetic variants for early detection.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},333467,1790951390,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","Journal of Hepatocellular Carcinoma Dovepress  \nopen access to scientific and medical research  \n Open Access Full Text Article  \nResearch Progress on the Role of Epigenetic Methylation Modification in Hepatocellular Carcinoma  \nREVIEW  \nJing Wang 1 , Wenyue Gao 1 , Hongbo Yu 1 , Yuting Xu 1 , Changchuan Bai2 , Qingwei Cong 1 , Ying Zhu 1  \n1Infectious Department, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 2Internal Department of Chinese Medicine, Dalian Hospital of Traditional Chinese Medicine, Dalian, Liaoning, 116013, People’s Republic of China  \nCorrespondence: Ying Zhu, Email [zhuyingsh52@126.com](zhuyingsh52@126.com)  \n\n| Abstract: Hepatocellular carcinoma (HCC) stands as the prevailing form of primary liver cancer, characterized by a poor prognosis and high mortality rate. A pivotal factor in HCC tumorigenesis is epigenetics, specifically the regulation of gene expression through methylation. This process relies significantly on the action of proteins that modify methylation, including methyltransferases, their associated binding proteins, and demethylases. These proteins are crucial regulators, orchestrating the methylation process by regulating enzymes and their corresponding binding proteins. This orchestration facilitates the reading, binding, detection, and catalysis of gene methylation sites. Methylation ences the development, prolisignificantly influferation, invasion, and prognosis of HCC. Furthermore, methylation modification and its regulatory mechanisms activate distinct biological characteristics in HCC cancer stem cells, such as inducing cancer-like differentiation of stem cells. They also influence the tumor microenvironment (TME) in HCC, modulate immune responses, affect chemotherapy resistance in HCC patients, and contribute to HCC progression through signaling pathway feedback. Given the essential role of methylation in genetic information, it holds promise as a potential tool for the early detection of HCC and as a target to improve drug resistance and promote apoptosis in HCC cells.\u003Cbr>Keywords: methylation modifying proteins, biomarkers, methyltransferases, HCC tumorigenesis |\n| --- |\n| Introduction\u003Cbr>Hepatocellular carcinoma (HCC), the predominant form of liver cancer, presents a significant global health challenge and is the fourth leading cause of cancer-related deaths. According to global cancer statistics, mortality from liver cancer accounts for 8.2% of all cancer-related deaths. The five-year survival rate for HCC and intrahepatic ductal carcinoma is 20.8% .1–3 Recent advancements in HCC management guidelines have significantly improved monitoring for high-risk groups and optimized tumor staging, leading to innovative approaches for early detection and improved prognosis. Despite the absence of uniform standards, personalized multimodal treatment strategies are increasingly recommended.3–5\u003Cbr>Epigenetics involves heritable gene expression patterns that do not alter the DNA sequence.6 The dysregulation of theepigenome becomes a key driver in the early development of HCC.7 Methylation regulation is an essential component of epigenetics, which is related to embryonic formation. In cancer, it encompassing DNA methylation, RNA methylation, histone methylation, and their respective modifiers. Various enzymes and binding proteins are essential for maintaining different methylation states.8–10 The combined use of databases with bisulfite detection and sequencing (BSP) for methylation studies is commonly used in experimental research, although some studies have also used techniques like MassARRAYEpiTYPER and Methylation-specific PCR (MSP) .11–13 Recent studies have underscored the potential of reversing epigenetic modifications through modifier inhibitors to restore normal cancer gene expression. This strategy offers promising therapeutic avenues to combat HCC.14 However, research into epigenetic methylation modification and target","cbCaine4rCF0KGNC","https://ap.wps.com/l/cbCaine4rCF0KGNC","pdf",1655821,14,"English","# Introduction\n## Epigenetics and methylation in HCC\n## Experimental approaches and therapeutic implications\n## Biomarkers and detection strategies","[{\"question\":\"What role does epigenetic methylation play in hepatocellular carcinoma (HCC)?\",\"answer\":\"Epigenetic methylation regulates gene expression without changing DNA sequence. Dysregulation of methylation in the epigenome is described as a driver in early HCC development and progression.\"},{\"question\":\"Which methylation-modifying proteins are emphasized as key regulators?\",\"answer\":\"The review highlights proteins that modify methylation, including methyltransferases, their associated binding proteins, and demethylases. These regulators coordinate enzymes and binding partners to govern methylation sites.\"},{\"question\":\"How does methylation contribute to HCC biomarkers and early detection?\",\"answer\":\"Aberrant methylation levels in HCC can occur in genes related to cell cycle, progression, and immune environment. The text also discusses non-invasive liquid biopsies using circulating tumor DNA and other methyl sequencing approaches to identify epigenetic variants for early detection.\"}]","Research Progress on the Role of Epigenetic Methylation Modification in Hepatocellular Carcinoma - Review | PDF",1790002596,35]