A circulating risk score, based on combination of exo-miR130a-3p and fibrinopeptide A, as predictive biomarker of relapse in early stage non-small cell lung cancer patients [miRNA]

To date, the 5-year overall survival of early stage non-small cell lung cancer (NSCLC) is still unsatisfactory at 59.8%. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on a double interconnection between cancer cells and the surrounding tumor microenvironment, and circulating molecules may represent promising markers of cancer recurrence. Here, we performed in-depth analysis of circolome-derived markers, including Exo-miRnome and peptidome in 67 radically resected NSCLCs, to identify a prognostic score. The miRnome profile selected exo-miR130a-3p as the most overexpressed in patients with relapse. Peptidome analysis identified 4 fibrinopeptide A (fpA), which were depleted in progressing patients. Notably, the combination of exo-miR130a-3p and the greatest fpA (2-16) built a score where high-risk patients had 24 months of disease-free survival. Moreover, in vitro transfections showed that higher levels of exo-miR-130a-3p lead to a deregulation of some pathways involved in metastasis, in angiogenesis, such as in coagulation. In conclusion, the identified risk score integrating circulating markers can help clinicians predict early-stage NSCLC patients who are more likely to relapse after initial surgery. A total of 67 resected NSCLC samples were analyzed to define a miRNA signature capable to predict patients who experience progression of the disease (PD).