Dados do Trabalho

Título

Molecular signature of miRNAs in cervical cancer patients exposed to pesticides

Introdução

The main risk factors for cervical cancer (CC), are well known, such as sexual history, long-term use of oral contraceptives, young age at first full-term pregnancy and mainly by high-risk Human Papillomavirus (hr-HPV) infection. Exposure to pesticides can also influence CC development, however, this association is poorly explored. Molecular signatures, like miRNAs profile in cervical, can be used to identify association between the exposure to pesticides and CC.

Objetivo

In this study, we aimed to identify miRNAs expression profile from liquid-based cytology (LBC) in patients with high-risk cervical precursor lesions exposed to pesticides.

Métodos

From a series of 54 patients (aged 25 to 64 years old) with high-risk cervical precursor lesions (CIN 2 and CIN 3), we selected 15 women exposed to pesticides (mean exposure time of 6.35 years) and 15 women not exposed to pesticides. We matched these two groups by age and smoking status. We performed miRNA expression profiling using the nCounter® miRNA Expression Assay (NanoString Technology), which evaluated 800 targets in LBC samples from 30 patients with cervical precursor lesions (15 exposed and 15 non-exposed individuals). This study was approved by the Barretos Cancer Hospital IRB (No. 1798/2019).

Resultados

We could determine the miRNA profile in LBC of all 30 participants. We identified 19 significantly expressed miRNAs between exposed and non-exposed group (p<0.01). All miRNAs were upregulated in the exposed comparison with non-exposed group. Moreover, using logistic regression analysis, we identified a signature composed of three miRNAs up-regulated in the exposed group (fold change ≥ 1.5 and p-value of ≤ 0.01), with a predictive value with an AUC of 0.867.

Conclusões

These findings suggest that exposure to pesticides can be identify in LBC by a miRNA signature. Further studies are needed to establish the association of pesticides with CC and validate the present molecular signature of exposure.

Palavras-chave

Cervical cancer; microRNAs; pesticides.

Financiador do resumo

Programa Nacional de Apoio à Atenção Oncológica (PRONON) under No. 25000.023997/2018-34.