{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T23:19:26Z","timestamp":1791674366738,"version":"4.3.4"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/00546 and PI17\/00772"],"award-info":[{"award-number":["PI15\/00546 and PI17\/00772"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Squamous intraepithelial lesions\/cervical intraepithelial neoplasias (SIL\/CIN) are high-risk human papilloma virus (hrHPV)-related lesions which are considered as high grade (HSIL\/CIN2-3) or low grade (LSIL\/CIN1) lesions according to their risk of progression to cervical cancer (CC). Most HSIL\/CIN2-3 are considered as transforming hrHPV infections, so truly CC precursors, although some clear spontaneously. hrHPV testing has a high sensitivity for the detection of HSIL\/CIN2-3 but a relatively low specificity for identifying transforming lesions. We aimed to determine whether the combination of CADM1, MAL and miR124 promoter methylation status assessed in histological samples can be used as a biomarker in the identification of transforming HSIL\/CIN lesions. Design: 131 cervical biopsies, including 8 cases with no lesion and a negative hrHPV test result (control group), 19 low-grade (L)SIL\/CIN1, 30 HSIL\/CIN2, 60 HSIL\/CIN3, and 14 CC were prospectively collected. hrHPV was detected and genotyped using the polymerase chain reaction (PCR)-based technique SPF10 HPV LIPA. A multiplex quantitative methylation-specific PCR (qMSP) was used to identify the methylation status of the CADM1, MAL, and miR124 promoter genes. Results: Significantly higher methylation levels of CADM1, MAL and miR-124 were found in HSIL\/CIN2-3 and CC compared with normal and LSIL lesions. DNA methylation of at least one gene was detected in 12.5% (1\/8) of normal samples, 31.5% (6\/19) of LSIL\/CIN1, 83.3% (25\/30) of HSIL\/CIN2, 81.6% (49\/60) of HSIL\/CIN3 and 100% (14\/14) of CC (p &lt; 0.001). The sensitivity and specificity for HSIL\/CIN2-3 and CC of having at least one methylated gene were 84.6% and 74.0%, respectively. The sensitivity and specificity of the combination of at least one methylated gene and a positive hrHPV test were 80.7% and 85.1% for HSIL\/CIN2-3 and CC, respectively. Conclusions: The methylation rate of CADM1, MAL and miR124 increases with the severity of the lesion. Further research is warranted to evaluate the usefulness of these biomarkers for the identification of transforming HSIL\/CIN.<\/jats:p>","DOI":"10.3390\/ijms20092262","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T08:19:59Z","timestamp":1557389999000},"page":"2262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2178-2403","authenticated-orcid":false,"given":"Marta","family":"del Pino","sequence":"first","affiliation":[{"name":"Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Sierra","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Marimon","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mart\u00ed Delgado","sequence":"additional","affiliation":[{"name":"Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Rodriguez-Trujillo","sequence":"additional","affiliation":[{"name":"Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Barnadas","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Saco","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aureli","family":"Torn\u00e9","sequence":"additional","affiliation":[{"name":"Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Ordi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"},{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.5858\/arpa.LGT200570","article-title":"The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and Consensus Recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology","volume":"136","author":"Darragh","year":"2012","journal-title":"Arch. 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