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 [Nanostring]

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 which could be linked to the FpA reduction. 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. A549 cells treated with miR130a-3p or miR17-5p. 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).