Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer

Autor(es):Mostrar menos -

Rogeri, Caroline Domingues ^[1] ; Santejo Silveira, Henrique Cesar ^[1] ; Causin, Rhafaela Lima ^[1] ; Villa, Luisa Lina ^{[2, 3]} ; Stein, Maira Degiovani ^[4] ; de Carvalho, Ana Carolina ^[1] ; Rebolho Batista Arantes, Lidia Maria ^[1] ; Scapulatempo-Neto, Cristovam ^[5] ; Possati-Resende, Julio Cesar ^[6] ; Antoniazzi, Marcio ^[6] ; Longatto-Filho, Adhemar ^{[7, 1, 8, 9]} ; Tavares Guerreiro Fregnani, Jose Humberto ^{[10, 1]}

Afiliação do(s) autor(es)

^[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Av Antenor Duarte Vilela 1331, BR-14784400 Barretos - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Radiol & Oncol, Sao Paulo - Brazil

^[3] ICESP Canc Inst State Sao Paulo, Sao Paulo - Brazil

^[4] Barretos Canc Hosp, Dept Pathol, Barretos - Brazil

^[5] DASA Diagnost Amer, Barueri - Brazil

^[6] Barretos Canc Hosp, Dept Prevent, Barretos - Brazil

^[7] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal

^[8] Minho Univ, Sch Med, Life & Hlth Sci Res Inst, ICVS, Braga - Portugal

^[9] Univ Sao Paulo, Sch Med, Dept Pathol, LIM14, Sao Paulo - Brazil

^[10] AC Camargo Canc Ctr, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: GYNECOLOGIC ONCOLOGY; v. 150, n. 3, p. 545-551, SEP 2018.
• Citações Web of Science: 5

Resumo

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 ON 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), LMXIA (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 613%, respectively) similar to that of the HPV test (913% 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 LMXIA (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 LMXIA genes may be a promising bio-marker for precursor lesions in cervical cancer regardless of the hr-HPV status. (C) 2018 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 15/15065-6 - Perfil de metilação de genes em lesões precursoras do câncer do colo do útero
• Beneficiário: Ursula Moraes Leme
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 12/51221-4 - Análise de sensibilidade especificidade de quatro algoritmos para o rastreamento do câncer do colo de útero combinando a citologia cervical e a pesquisa molecular do papilomavírus humano (HPV)
• Beneficiário: Adhemar Longatto Filho
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisa em Políticas Públicas para o SUS
• Processo FAPESP: 14/24415-8 - Perfil de metilação de genes em lesões precursoras do câncer do colo do útero
• Beneficiário: Caroline Domingues Rogeri
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 14/50014-0 - Perfil de metilação de genes em lesões precursoras do câncer do colo do útero
• Beneficiário: José Humberto Tavares Guerreiro Fregnani
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisa em Políticas Públicas para o SUS