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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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]
Total Authors: 12
Affiliation:
[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
Total Affiliations: 10
Document type: Journal article
Source: GYNECOLOGIC ONCOLOGY; v. 150, n. 3, p. 545-551, SEP 2018.
Web of Science Citations: 5
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; 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)

FAPESP's process: 12/51221-4 - Analysis of sensitivity and specificity of four algorithms for cervical cancer screening combining cervical cytology and Human Papillomavirus molecular test (HPV)
Grantee:Adhemar Longatto Filho
Support Opportunities: Research Grants - Research in Public Policies for the National Health Care System (PP-SUS)
FAPESP's process: 14/50014-0 - Genes methylation profile in uterine cervical cancer precursor lesions
Grantee:José Humberto Tavares Guerreiro Fregnani
Support Opportunities: Research Grants - Research in Public Policies for the National Health Care System (PP-SUS)