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dc.contributor.authorRogeri, Caroline Dominguespor
dc.contributor.authorSilveira, Henrique César Santejopor
dc.contributor.authorCausin, Rhafaela Limapor
dc.contributor.authorVilla, Luisa Linapor
dc.contributor.authorStein, Maíra Degiovanipor
dc.contributor.authorde Carvalho, Ana Carolinapor
dc.contributor.authorArantes, Lídia Maria Rebolho Batistapor
dc.contributor.authorScapulatempo-Neto, Cristovampor
dc.contributor.authorPossati-Resende, Júlio Césarpor
dc.contributor.authorAntoniazzi, Márciopor
dc.contributor.authorLongatto, Adhemarpor
dc.contributor.authorFregnani, José Humberto Tavares Guerreiropor
dc.identifier.citationRogeri, C. D., Silveira, H. C. S., Causin, R. L., Villa, L. L., Stein, M. D., de Carvalho, A. C., ... & Longatto-Filho, A. (2018). Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer. Gynecologic oncology, 150(3), 545-551por
dc.description.abstractThe methylation profile of genes in precursor lesions in cervical cancer was characterized to improve screening techniques for high-grade intraepithelial neoplasia.por
dc.description.abstractObjectives The methylation profile of genes in precursor lesions in cervical cancer was characterized to improve screening techniques for high-grade intraepithelial neoplasia. Methods A total of 447 cervical cytology samples obtained from women who underwent colposcopy were examined. The cases were distributed as follows: (1) cervices without cervical intraepithelial neoplasia (CIN; n = 152); (2) cervices with a CIN grade of 1 (CIN 1; n = 147); and (3) cervices with a CIN grade of 2 or 3 (CIN 2/3; n = 148). The methylation pattern for a panel of 15 genes was analysed by quantitative methylation-specific PCR (qMSP) and compared between the groups (≤CIN 1 vs. CIN 2+). Results In the validation set, seven genes presented significantly different methylation profiles according to diagnosis, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), HIC1 (p = 0.028), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). Six genes showed a significant increase in the frequency of methylation in the presence of hr-HPV, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). The methylation of the hsa-miR-124 gene showed sensitivity and specificity (86.7% and 61.3%, respectively) similar to that of the HPV test (91.3% and 50.0%, respectively). The independent factors associated with the diagnosis of CIN 2+ and the methylation of the hsa-miR-124-2 (OR = 5.1), SOX1 (OR = 2.8), TERT (OR = 2.2), and LMX1A (OR = 2.0) genes were a positive test for hr-HPV (odds ratio [OR] = 5.5). Conclusions Hypermethylation of the hsa-miR-124-2, SOX1, TERT, and LMX1A genes may be a promising biomarker for precursor lesions in cervical cancer regardless of the hr-HPV status.por
dc.description.sponsorshipSão Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo–FAPESP) with the cooperation of the Coordination for the Improvement of Higher Education Personnel (Conselho Nacional de Desenvolvimento Científico e Tecnológico–CNPq-PPSUS) (Protocol Nos. 12/51221-4, 14/50014-0, 14/24415-8, and 15/15065-6), the National Institute of Science and Technology (Instituto Nacional de Ciência e Tecnologia–INCT-HPV) (FAPESP Proc. No. 2008/578891 and CNPq Proc. No. 573799/2008-3), and CAPES (PROSUP/CAPES Protocol No. 1571815)por
dc.subjectBiomarkers, Tumorpor
dc.subjectCervical Intraepithelial Neoplasiapor
dc.subjectEarly Detection of Cancerpor
dc.subjectLIM-Homeodomain Proteinspor
dc.subjectMiddle Agedpor
dc.subjectPapillomavirus Infectionspor
dc.subjectPromoter Regions, Geneticpor
dc.subjectSOXB1 Transcription Factorspor
dc.subjectSensitivity and Specificitypor
dc.subjectTranscription Factorspor
dc.subjectUterine Cervical Neoplasmspor
dc.subjectDNA Methylationpor
dc.subjectCervical cancer preventionpor
dc.subjectCervical cytologypor
dc.subjectHuman papillomaviruspor
dc.subjectTumour suppressor genespor
dc.titleMethylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancerpor
dc.subject.fosCiências Médicas::Medicina Básicapor
dc.subject.wosScience & Technologypor
sdum.journalGynecologic Oncologypor
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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