Genes methylation profile in uterine cervical cancer precursor lesions

• Grant number: 14/50014-0
• Support Opportunities: Research Grants - Research in Public Policies for the National Health Care System (PP-SUS)
• Start date: July 01, 2014
• End date: March 31, 2016
• Field of knowledge: Health Sciences - Collective Health - Preventive Medicine
• Agreement: CNPq - PPSUS
• Principal Investigator: José Humberto Tavares Guerreiro Fregnani
• Grantee: José Humberto Tavares Guerreiro Fregnani
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Aims: 1) To evaluate and compare the methylation profile of 15 genes of the host and 3 of HPV16 in cervical cytology samples from women with and without CIN; 2) To compare the accuracies of molecular methods (methylation and HPV test) for diagnosing CIN2 and CIN3. Materials and methods: It will be included 350 samples of cervical cytology from women who underwent colposcopy in Barretos Cancer Hospital. Cases will be distributed as follows: cervix without CIN (n=150), CIN1 (n=100), CIN2 (n=50) and CIN3 (n=50). Cervical cytology will provide aliquots for the molecular analyses. The HPV test will be performed on Cobas X480™ (Roche Molecular Systems, USA). Methylation analysis will include a panel with 15 host genes (HIC1, APC, Cadml, CDH, DAPK1, TERT, JAM3, EPB41L3, C130RF18, MAL, hsa-miR-124-2, SOX1, PAX1, Lmxla and NKX6-1) and 4 genes of HPV16 (L1, L2 and HPV16 E2/E4) by Real Time PCR (Quantitative methylation Specific PCR - QMSP). The frequency of methylation of each gene will be compared between groups (5 NIC1 vs. CIN2/CIN3) using the Fisher's exact test. Accuracies of each molecular testing (methylation and HPV test) will be measured and compared by means of sensitivity, specificity, predictive values (positive and negative) and area under the ROC curve. Expected results and applications: Some of the methylated genes (or their combination) may be useful as biomarkers of precursor lesions of cervical cancer in liquid based cytology. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROGERI, CAROLINE DOMINGUES; SANTEJO SILVEIRA, HENRIQUE CESAR; CAUSIN, RHAFAELA LIMA; VILLA, LUISA LINA; STEIN, MAIRA DEGIOVANI; DE CARVALHO, ANA CAROLINA; REBOLHO BATISTA ARANTES, LIDIA MARIA; SCAPULATEMPO-NETO, CRISTOVAM; POSSATI-RESENDE, JULIO CESAR; ANTONIAZZI, MARCIO; et al. Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer. GYNECOLOGIC ONCOLOGY, v. 150, n. 3, p. 545-551, SEP 2018. (12/51221-4, 14/50014-0)