Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related death. Worldwide, about 20% of cases are diagnosed at an early stage, allowing an effective pulmonary resection. However, lung cancer 5-years survival rate remains below 16% mainly because of disseminated disease, also in fully resected early stages. Biomarkers able to identify patients with a higher risk of relapse could be very useful. Circulating microRNAs (miRNAs), in both exosome-free and exosome-encapsulated forms, represent promising markers in this setting. Some studies in the literature and our preliminary data have shown that specific miRNA signatures could have a prognostic role in NSCLC, both in the early-stage and in the metastatic disease. Moreover, free circulating DNA (fcDNA) is another prognostic marker in advanced NSCLC, whereas its role in earlystage lung cancer is not so clear yet.

We hypothesize that exosomal and/or circulating miRNAs could represent prognostic biomarkers in resected-early-stage NSCLC and that a different expression profile at baseline, before surgery, could be indicative of a different patient survival. We also hypothesize that fcDNA could also be, singly or in combination with exosomal/circulating miRNAs, a prognostic biomarker in this setting.