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.
Highlights
Lung cancer, predominantly non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths worldwide [1]
The aim of our study was to: 1) select a large panel of miRNAs that have been reported to be highly deregulated in NSCLC, 2) determine whether the plasma expression profiles of these miRNAs were altered in NSCLC patients compared to healthy individuals and 3) evaluate whether the miRNA profile is able to predict the prognosis of resectable NSCLC
Levels of expression of plasma miRNAs Based on the literature, we selected seventeen miRNAs reported to be most frequently altered in primary NSCLC patients (Table S1)
Summary
Predominantly non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths worldwide [1]. The poor prognosis of NSCLC patients is largely due to the lack of routine, validated, effective and low cost screening tools that allow detection of early-stage tumors. Developing such biomarkers is a public health imperative since diagnosis and treatment of early-stage NSCLC is associated with 60–80% survival at 5 years [1,3]. A large variability in disease outcome has been observed for a subset of patients with similar clinical and pathological features, the current staging system may be insufficient to consistently predict the treatment outcome of NSCLC [4]. Prognostic assessment of the patients is essential to choose the best therapeutic strategy and may be improved by the integration of new robust prognostic biomarkers
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