Molecular signatures of microRNAs in precursor lesions of cervical cancer

• Grant number: 16/15831-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2017
• End date: December 31, 2018
• Field of knowledge: Health Sciences - Collective Health - Epidemiology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Márcia Maria Chiquitelli Marques Silveira
• Grantee: Rhafaela Lima Causin
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Background: There are numerous and well-documented evidence in the literature showing that cervical cytology is limited as a single method for the screening of cervical cancer. Therefore, there is need to incorporate molecular tests to improve the accuracy of detection of premalignant lesions, such as seems to be the evaluation of changes in microRNAs (miRNAs). The analysis of microRNAs differential would allow the expansion of diagnostic testing arsenal for the screening of Cervical Intraepithelial Neoplasia (CIN). Aim: 1) Achieve analysis of association between microRNA expression, the presence of HPV and genotyping; 2) Identify and compare the profile of miRNA expression by nCouter miRNA Expression Assays panel (800 targets) for NanoString in cervical cytology samples from women with and without CIN; 3) Validate the expression profile of host microRNAs by digital PCR technology; 4) Assess the accuracies of molecular testing expression of miRNAs identified as differentially expressed in intraepithelial neoplasia prediction of high-grade and compare them with the molecular HPV test. Materials and methods: will be included 350 samples stored cervical cytology of women who underwent colposcopy at Barretos Cancer Hospital. The cases will be distributed as follows: cervix without CIN (n = 150), CIN1 (n = 100), CIN2 (50) and CIN3 (50). Cervical cytology provide rates for the molecular analyzes. The HPV test will be held at Cobas X480 " system (Roche Molecular Systems, USA). Previously we will perform perliminar analysis of the expression of microRNAs panel nCounter® miRNA Expression Assays (NanoString Technologies, Seattle, WA, USA) with 800 microRNAs host with the following distribution CIN (n = 10), CIN1 (n = 10), CIN2 (n = 10) and CIN3 (n = 10), then the microRNAs that show as accurate will be validated by digital PCR technology in the full population. The expression profile of differentially expressed miRNAs will be compared between groups (d NIC1 vs. CIN2 / CIN3) using dedicated tools R / Bioconductor. The accuracies of each of the molecular testing (microRNAs and HPV test) will be measured and compared by sensitivity, specificity, predictive values (positive and negative) and area under the ROC curve. Results and applications: Some of the microRNAs identified as differentially expressed may be used as biomarkers of precursor lesions from cervical cancer in cervical cytology specimens preserved in liquid foundation. If these biomarkers show as much (or more) accurate than molecular analysis of HPV, they may represent a new form of early diagnosis of precursor lesions of cervical cancer. (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)

CAUSIN, RHAFAELA LIMA; PESSOA-PEREIRA, DANIELLE; BORBA SOUZA, KAREN CRISTINA; EVANGELISTA, ADRIANE FEIJO; VIEIRA REIS, RUI MANUEL; TAVARES GUERREIRO FREGNANI, JOSE HUMBERTO; CHIQUITELLI MARQUES, MARCIA MARIA. Identification and performance evaluation of housekeeping genes for microRNA expression normalization by reverse transcription-quantitative PCR using liquid-based cervical cytology samples. Oncology Letters, v. 18, n. 5, p. 4753-4761, NOV 2019. (16/15831-3)

CAUSIN, RHAFAELA LIMA; FREITAS, ANA JULIA AGUIAR DE; TROVO HIDALGO FILHO, CASSIO MURILO; REIS, RICARDO DOS; REIS, RUI MANUEL; MARQUES, MARCIA MARIA CHIQUITELLI. A Systematic Review of MicroRNAs Involved in Cervical Cancer Progression. CELLS, v. 10, n. 3, MAR 2021. (16/15831-3)

CAUSIN, RHAFAELA L.; DA SILVA, LUCIANE S.; EVANGELISTA, ADRIANE F.; LEAL, LETICIA F.; SOUZA, KAREN C. B.; PESSOA-PEREIRA, DANIELLE; MATSUSHITA, GRAZIELA M.; REIS, RUI M.; FREGNANI, JOSE H. T. G.; MARQUES, MARCIA M. C.. MicroRNA Biomarkers of High-Grade Cervical Intraepithelial Neoplasia in Liquid Biopsy. BIOMED RESEARCH INTERNATIONAL, v. 2021, APR 14 2021. (16/15831-3)