{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:35Z","timestamp":1787028575180,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Second Century Fund (C2F), Chulalongkorn University"},{"name":"The Ratchadaphiseksomphot Endowment Fund","award":["65413000120839 RCU_68_025_3000_001"],"award-info":[{"award-number":["65413000120839 RCU_68_025_3000_001"]}]},{"name":"The 90th Anniversary of Chulalongkorn University Scholarship, Ratchadapiseksompotch Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anal cancer is high in men who have sex with men living with human immunodeficiency virus (MSM-LWHIV). This cancer is strongly associated with high-risk human papillomavirus (HR-HPV) infection. Anal cancer screening using cytology and high-resolution anoscopy (HRA) for diagnosis of anal intraepithelial neoplasia requires specialized expertise. Biomarkers for the diagnosis of abnormal anal cells are of interest. Thyrotropin-releasing hormone (TRH) methylation at cg01009664 was detected using a pyrosequencing assay to compare methylation patterns among different anal lesions. Our results demonstrated that TRH methylation was significantly hypermethylated in anal intraepithelial neoplasia (AIN3) (&gt;20%) and AIN1-2 (&gt;10%) but less methylated in normal (&lt;10%) (p &lt; 0.001). TRH gene methylation showed higher sensitivity than the cytology for predicting AIN1+ (75.96% vs. 25.37%, respectively) and AIN2+ (78.95%% vs. 19.23%, respectively). There was no significant correlation between TRH methylation and the percentage of CD4 in patients with HIV (p &gt; 0.05). TRH methylation in anal swabs reflects the presence of anal intraepithelial neoplasia. Methylation analysis showed higher sensitivity than cytology for high-grade lesions and was independent of immune status. These findings support its use as a screening tool to preselect patients for HRA, potentially reducing unnecessary procedures while maintaining diagnostic accuracy.<\/jats:p>","DOI":"10.3390\/ijms262411784","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T15:11:24Z","timestamp":1764947484000},"page":"11784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Thyrotropin-Releasing Hormone Gene Methylation as a Potential Biomarker for Anal Intraepithelial Neoplasia"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4106-351X","authenticated-orcid":false,"given":"Chavis","family":"Pholpong","sequence":"first","affiliation":[{"name":"Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Applied Medical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nittaya","family":"Phanuphak","sequence":"additional","affiliation":[{"name":"Institute of HIV Research and Innovation, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tippawan","family":"Pankam","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, College of Allied Health Sciences, Rattana Bundit University, Pathum Thani 12160, Thailand"},{"name":"The Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supranee","family":"Buranapraditkun","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Department of Medicine, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Thai Red Cross Society, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center\u2014Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakarin","family":"Kitkumthorn","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernett","family":"Lee","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvapan","family":"Bhattarakosol","sequence":"additional","affiliation":[{"name":"Center of Excellence in Applied Medical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkom","family":"Chaiwongkot","sequence":"additional","affiliation":[{"name":"Center of Excellence in Applied Medical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/ijc.33185","article-title":"A meta-analysis of anal cancer incidence by risk group: Toward a unified anal cancer risk scale","volume":"148","author":"Clifford","year":"2021","journal-title":"Int. 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