Two panels of plasma microRNAs as non-invasive biomarkers for prediction of recurrence in resectable NSCLC

Abstract

The diagnosis of non-small cell lung carcinoma (NSCLC) at an early stage, as well as better prediction of outcome remains clinically challenging due to the lack of specific and robust non-invasive markers. The discovery of microRNAs (miRNAs), particularly those found in the bloodstream, has opened up new perspectives for tumor diagnosis and prognosis. The aim of our study was to determine whether expression profiles of specific miRNAs in plasma could accurately discriminate between NSCLC patients and controls, and whether they are able to predict the prognosis of resectable NSCLC patients. We therefore evaluated a series of seventeen NSCLC-related miRNAs by quantitative real-time (qRT)-PCR in plasma from 52 patients with I-IIIA stages NSCLC, 10 patients with chronic obstructive pulmonary disease (COPD) and 20-age, sex and smoking status-matched healthy individuals. We identified an eleven-plasma miRNA panel that could distinguish NSCLC patients from healthy subjects (AUC = 0.879). A six-plasma miRNA panel was able to discriminate between NSCLC patients and COPD patients (AUC = 0.944). Furthermore, we identified a three-miRNA plasma signature (high miR-155-5p, high miR-223-3p, and low miR-126-3p) that significantly associated with a higher risk for progression in adenocarcinoma patients. In addition, a three-miRNA plasma panel (high miR-20a-5p, low miR-152-3p, and low miR-199a-5p) significantly predicted survival of squamous cell carcinoma patients. In conclusion, we identified two plasma miRNA expression profiles that may be useful for predicting the outcome of patients with resectable NSCLC.

Figure 1. Heat-map clustering analysis of the deregulated miRNA expression levels of NSCLC patients, COPD patients and healthy individuals.

Average linkage and 1-Pearson correlation as distance metric were used for the clustering.

Figure 2. Kaplan-Meier DFS curves for lung adenocarcinoma patients

(upper panels) and lung squamous cell carcinoma patients (lower panels) stratified according to plasma levels of miR-155-5p (A), miR-223-3p (B), miR-126-3p (C), miR-152-3p (D), miR-20a-5p (E), and miR-199a-5p (F). The P-values were calculated using the log-rank test between patients with high- and low-fold changes.