Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/58255

TitleMethylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer
Author(s)Rogeri, Caroline Domingues
Silveira, Henrique César Santejo
Causin, Rhafaela Lima
Villa, Luisa Lina
Stein, Maíra Degiovani
de Carvalho, Ana Carolina
Arantes, Lídia Maria Rebolho Batista
Scapulatempo-Neto, Cristovam
Possati-Resende, Júlio César
Antoniazzi, Márcio
Longatto, Adhemar
Fregnani, José Humberto Tavares Guerreiro
KeywordsAdult
Biomarkers, Tumor
Cervical Intraepithelial Neoplasia
Early Detection of Cancer
Female
Humans
LIM-Homeodomain Proteins
MicroRNAs
Middle Aged
Papillomaviridae
Papillomavirus Infections
Promoter Regions, Genetic
SOXB1 Transcription Factors
Sensitivity and Specificity
Telomerase
Transcription Factors
Uterine Cervical Neoplasms
DNA Methylation
Cervical cancer prevention
Cervical cytology
Human papillomavirus
Tumour suppressor genes
Issue dateSep-2018
PublisherElsevier
JournalGynecologic Oncology
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), 545-551
Abstract(s)The methylation profile of genes in precursor lesions in cervical cancer was characterized to improve screening techniques for high-grade intraepithelial neoplasia.
Objectives 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.
TypeArticle
URIhttp://hdl.handle.net/1822/58255
DOI10.1016/j.ygyno.2018.06.014
ISSN0090-8258
e-ISSN1095-6859
Publisher versionhttps://www.sciencedirect.com/science/article/pii/S0090825818309909
Peer-Reviewedyes
AccessRestricted access (UMinho)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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