Analysis of extracellular-vesicle miRNAs in a new aggressive molecular subtype of lung cancer

Non-Small Cell Lung cancer is the most frequently diagnosed lung cancer type (80-90%) and lung adenocarcinoma (LUAD) is the major subtype. Early diagnosis by low-dose computed tomography was shown to be effective in reducing mortality (~20% at 5 years). However, the management of lung cancer patients can be difficult due to pathological and genetic heterogeneity of the disease. We discovered a new molecular subtype namely C1-LUAD using a 10-genes signature, which correlates with the worst prognosis and has peculiar features of mesenchymal and stem-like cells. Of note, analyzing intracellular differentially expressed miRNAs in C1 patients, we found a targeted network of genes as hubs of mechanisms for lung cancer progression. Moreover, we discovered 5 miRNAs up-regulated and 6 miRNAs down-regulated in C1 exosomes extracted from serum, which pave the way to make an early diagnosis for this aggressive subtype of LUAD. Finally, we highlighted that C1-like cells are more prone to internalized labeled-exosomes in a time and dose dependent manner, suggesting a role of these extracellular-vesicles in the maintenance of the metastatic features.