Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer.
Gynecol Oncol
; 150(3): 545-551, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-29960712
ABSTRACT
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; nâ¯=â¯152); (2) cervices with a CIN grade of 1 (CIN 1; nâ¯=â¯147); and (3) cervices with a CIN grade of 2 or 3 (CIN 2/3; nâ¯=â¯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 (pâ¯=â¯0.001), EPB41L3 (pâ¯=â¯0.001), HIC1 (pâ¯=â¯0.028), hsa-miR-124-2 (pâ¯=â¯0.001), LMX1A (pâ¯=â¯0.001), SOX1 (pâ¯=â¯0.001), and TERT (pâ¯=â¯0.001). Six genes showed a significant increase in the frequency of methylation in the presence of hr-HPV, namely, DAPK1 (pâ¯=â¯0.001), EPB41L3 (pâ¯=â¯0.001), hsa-miR-124-2 (pâ¯=â¯0.001), LMX1A (pâ¯=â¯0.001), SOX1 (pâ¯=â¯0.001), and TERT (pâ¯=â¯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 (ORâ¯=â¯5.1), SOX1 (ORâ¯=â¯2.8), TERT (ORâ¯=â¯2.2), and LMX1A (ORâ¯=â¯2.0) genes were a positive test for hr-HPV (odds ratio [OR]â¯=â¯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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Displasia do Colo do Útero
/
Neoplasias do Colo do Útero
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Metilação de DNA
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Screening_studies
Limite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article