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Because tumor suppressor gene hypermethylation is an early event in NPC, whole-genome methylation sequencing of plasma cell-free DNA (cfDNA) from NPC cases and healthy controls was performed, integrating Illumina Human Methylation 450K array data. A cell-type-regulated CpG island in VILL (Vilin Like) was identified and validated across GEO and TCGA cohorts. A methylation-specific qPCR (qMSP) assay for VILL was tested in primary NPC and NC plasma, and combined with EBV DNA detection to improve early-stage sensitivity.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/plasma-cfdna-vill-gene-methylation-as-a-diagnostic-marker-for-nasopharyngeal-carcinoma/364564/",{"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/plasma-cfdna-vill-gene-methylation-as-a-diagnostic-marker-for-nasopharyngeal-carcinoma/364564.png","ImageObject",300,407,{"name":92,"@type":93},"Oliver","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is diagnostic sensitivity a key challenge for nasopharyngeal carcinoma?","Question",{"text":113,"@type":114},"Non-invasive diagnostic approaches for NPC struggle with low sensitivity, contributing to delayed diagnosis. The document emphasizes that early-stage detection is difficult with current methods.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What role does VILL gene methylation play in the study?",{"text":118,"@type":114},"Whole-genome methylation analyses identified a CpG island within the tumor suppressor gene VILL that shows specific methylation patterns in NPC. The study validates this finding across multiple datasets.",{"name":120,"@type":111,"acceptedAnswer":121},"How does the combined testing approach improve diagnostic accuracy?",{"text":122,"@type":114},"VILL methylation assessment using a qMSP system is compared with EBV DNA qPCR, and a combined methodology increases sensitivity. The document reports improved sensitivity for both overall NPC and early-stage NPC when used together.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},364564,1790216806,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"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},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Fu et al. Clinical Epigenetics (2025) 17:38 [https://doi.org/10.1186/s13148-025-01847-7](https://doi.org/10.1186/s13148-025-01847-7)  \nClinical Epigenetics  \n RESEARCH Open Access  \nPlasma cfDNAVILL gene methylation  as a diagnostic marker for nasopharyngeal carcinoma  \nXiao‑Yan Fu 1,2*, Zi‑Ying Zhou3, Teng‑Yue Yang4, Ying‑Juan Wen5, Da‑Bo Liu 1,2*, Yi‑Bo Zhou6*, Yuan Yue7*, Fei Ye7* and Zhong‑Xi Huang3*  \nAbstract  \nCurrently, the non‑invasive diagnostic methods for nasopharyngeal carcinoma (NPC) continue to grapple  \nwith the challenge of low sensitivity. The hypermethylation of tumor suppressor genes is an established early event in NPC pathogenesis. Consequently, we conducted whole‑genome methylation sequencing on plasma cell‑free DNA (cfDNA) from six NPC cases and four healthy controls, integrating Illumina Human Methylation 450 K microarray data from the GEO database comprising six NPC cases and six samples of non‑cancerous nasopharyngeal tissue (NP) . As result, we screened only one CpG island associated with cell type‑specific regulation within the candidate tumor suppressor gene VILL (Vilin Like), which exhibits specific methylation patterns in NPC. We validated our findings using 25 pairs of NPC and NP samples from GEO, alongside 9,736 pan‑cancer tissues from TCGA and 656 healthy human leukocyte samples sourced from GEO through methylation microarray analysis. Based on this, we designed a methylation‑specific qPCR (qMSP) system for theVILL gene, and then tested it on 192 primary NPC and 154 NC plasma samples. The new qMSP system when compared with EBV DNA qPCR revealed a sensitivity for primary NPC of 80 . 2% vs.81. 3%(78 . 8% vs.54. 5% for early‑stage NPC), and a specificity of 100% vs. 93. 5% . Notably, employing a combined methodology further enhanced sensitivity to 94 . 8%, including a sensitivity rate of 90 . 9% for early‑stage NPC diagnosis. Therefore, VILL methylation assessment combined with EBV DNA detection presents a promising avenue for non‑invasive diagnosis of NPC, particularly beneficial for early detection.  \nKeywords Nasopharyngeal carcinoma (NPC), Cell‑free DNA (cfDNA), VILL, DNA methylation, Diagnosis  \n*Correspondence: Xiao‑Yan Fu [1390160721@qq.com](1390160721@qq.com)[ ](1390160721@qq.com)Da‑Bo Liu [daboliu@mailnesia.com](daboliu@mailnesia.com)[ ](daboliu@mailnesia.com)Yi‑Bo Zhou [boyi365@163.com](boyi365@163.com)[ ](boyi365@163.com)Yuan Yue [yuanyue_keyan@126.com](yuanyue_keyan@126.com)[ ](yuanyue_keyan@126.com)Fei Ye  \n[yefei5620@163.com](yefei5620@163.com)[ ](yefei5620@163.com)Zhong‑Xi Huang [zxhuang@smu.edu.cn](zxhuang@smu.edu.cn)  \n1 Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, China  \n2 The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China  \n3 Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China  \n4 Huizhou Health Sciences Polytechnic, Huizhou 516025, China  \n5 Department of Radiotherapy, General Hospital of Southern Theatre Command of PLA, Guangzhou 510010, China  \n6 Department of Otolaryngology Head and Neck Surgery, Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha 410010, China  \n7 Department of Otolaryngology Head and Neck Surgery, Zhongshan City People’s Hospital, Zhongshan City 528400, Guangdong Province, China  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution‑NonCommercial‑NoDerivatives 4.0 International License, which permits any non‑commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this articl","cbCaiaNIZTDIAbFq","https://ap.wps.com/l/cbCaiaNIZTDIAbFq","pdf",2409346,"English","# Background\n## Clinical problem and current diagnostic limits\n# Methods\n## Whole-genome methylation sequencing and dataset integration\n## Validation cohorts\n## Development of VILL methylation-specific qPCR (qMSP)\n# Results\n## Methylation screening and VILL-specific pattern\n## Diagnostic performance vs. EBV DNA qPCR\n## Combined strategy for improved sensitivity","[{\"question\":\"Why is diagnostic sensitivity a key challenge for nasopharyngeal carcinoma?\",\"answer\":\"Non-invasive diagnostic approaches for NPC struggle with low sensitivity, contributing to delayed diagnosis. The document emphasizes that early-stage detection is difficult with current methods.\"},{\"question\":\"What role does VILL gene methylation play in the study?\",\"answer\":\"Whole-genome methylation analyses identified a CpG island within the tumor suppressor gene VILL that shows specific methylation patterns in NPC. The study validates this finding across multiple datasets.\"},{\"question\":\"How does the combined testing approach improve diagnostic accuracy?\",\"answer\":\"VILL methylation assessment using a qMSP system is compared with EBV DNA qPCR, and a combined methodology increases sensitivity. The document reports improved sensitivity for both overall NPC and early-stage NPC when used together.\"}]","Plasma cfDNA VILL Gene Methylation as a Diagnostic Marker for Nasopharyngeal Carcinoma | PDF",1790158193,25]