Role of Circulating Mirnas As Prognostic Biomarkers in Resected Early-Stage Non-Small Cell Lung Cancer

Background: Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related death, with a 5-year survival rate < 16% mainly because of disseminated disease, even in fully resected early-stage disease. Biomarkers identifying patients at a higher risk of relapse would be useful and circulating microRNAs (miRNAs) are a promising option in this setting. Methods: We analyzed a case series of 182 patients with resected early stage (IA-IIIA) NSCLC (99 adenocarcinoma [ADC] and 83 squamous cell carcinoma [SCC]). Peripheral blood samples were collected from each patient before surgical resection and serum was obtained after centrifugation and stored at -80 °C until miRNA extraction. A panel of 84 circulating miRNAs was analyzed by Real Time PCR. Data were normalized using an external spike-in (cel-miR-39) and the mean of the two most stable endogenous housekeeping genes chosen separately for ADC and SCC samples. miRNA expression was analyzed in relation to disease-free survival (DFS) by the Cox regression model. Results are reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In ADC patients, stage was significantly associated with DFS (HR stage II-IIIA vs stage I = 4.94, 95% CI [2.71 - 9.02]). Multiple statistical methods were used to evaluate miRNA expression data. In univariate analysis, two miRNAs (miR-222-3p and miR-22-3p) were significantly associated with DFS (p = 0.033 and p = 0.041, respectively). However, this significance was not maintained after adjusting for multiple testing. In SCC patients, disease stage was significantly related to DFS (HR stage II-IIIA vs stage I = 3.31, 95% CI [1.74 - 6.33]). Five miRNAs (let-7a-5p, miR-126-3p, miR-26a-5p, miR-130b-3p, miR-21-5p) were significantly associated with DFS even after adjusting for multiple testing (False Discovery Rate q-value <0.001). Conclusions: Pre-surgery circulating levels of let-7a-5p, miR-126-3p, miR-26a-5p, miR-130b-3p and miR-21-5p would appear to be significantly correlated with prognosis in resected early-stage SCC. Legal entity responsible for the study: IRST-IRCCS Funding: None Disclosure: All authors have declared no conflicts of interest.