Identification of miRNA-based biomarkers for screening and early detection of lung cancer

Abstract

Lung cancer is the most prevalent type of cancer worldwide and the most lethal. The high mortality rate from lung cancer is due to the fact that most cases are diagnosed in advanced stages of the disease when treatment is ineffective. For this reason, screening programs have been deployed worldwide in an attempt to reduce lung cancer mortality rates. Currently, strategies based on the analysis of body fluids (liquid biopsy) have been increasingly used, however, the application of this type of analysis in screening programs remains incipient. The detection of free circulating miRNAs (cfmiRNAs) in plasma, serum, urine and saliva samples is promising thanks to the stability of these molecules in different body fluids. In this way, the present study intends to identify, in biopsy samples, diagnostic biomarkers based on microRNAs in a case-control study. Objective: Identify miRNA-based biomarkers for screening and early detection of lung cancer in samples obtained using minimally invasive procedures. Materials and methods: Plasma and sputum samples will be evaluated in a group of control subjects (n = 50) and a group of cases (n = 50) diagnosed with non-small cell lung cancer (NSCLC), both attended by the cancer screening program. lung in a mobile unit of the Barretos Cancer Hospital or in a fixed unit of the Barretos Cancer Hospital. Plasma and sputum samples will be subjected to RNA extraction (Norgen Plasma / Serum Circulating and Exosomal RNA Purification Kit, Cat. #42800), followed by an analysis of the miRNA expression profile (nCounter miRNA Expression Human v3) by the NanoString platform. The expression results will be normalized and, for differential expression analysis, filters will be performed to exclude miRNAs with no expression (missing), with a fold change difference less than 2 and with a p-value greater than 0.05. In order to assess the detection potential of the selected miRNAs in the samples of body fluids, sensitivity, specificity, accuracy, positive and negative predictive values will be calculated. Expected Results: It is expected to define a panel of specific miRNAs with high sensitivity and high specificity in body fluids of patients with lung cancer when compared to people without cancer and exposed to the same risk factors. The miRNA panel resulting from this study can be used for the early diagnosis of lung cancer without the need for invasive procedures. (AU)