Prognostic Impact of a 3-MicroRNA Signature on Cytological Samples of Small-Cell Lung Cancer and on Surgical Samples of Squamous Cell Carcinoma of the Lung

Lung cancer is currently the most common malignancy and the leading cause of cancerrelated death worldwide. There are two main types: small cell lung cancer (SCLC) and nonsmall lung cancer (NSCLC). As revealed by recent genome-wide studies, individual lung tumors also possess highly diverse genomes, which further underscore the biological complexity of these diseases. Untangling the relationship between lung tumor histotype, phenotype and molecular heterogeneity represents a critical barrier in improving the clinical outcome of thoracic malignancies, which collectively account for most cancer-related deaths to date. Evidences from multiple tumour types and model systems implicate miRNA dysregulation as a common mechanism of tumorigenesis. Besides miRNAs are more stable than other biomarkers during sample processing, thus more suitable for analysis in tissue sample. Moreover, we have investigated whether the expression of a 3-miRNA panel could be a useful prognostic biomarker in lung cancer patients. The aims were the evaluation of the feasibility of miRNA extraction in cytological clinical (n= 50, SCLC) and surgical samples Squamous Cell Carcinoma (n=86; SCC) of lung, and the possible influence of the different types of fixative solution in the preservation of the integrity of miRNA. Moreover, we tried to identify a panel of miRNAs possibly useful in clinical practice as prognostic and /or predictive biomarkers. In SCLC, multivariate Cox analysis indicated that 3-miRNA panel was independently associated with survival, and in the group of older patients could discriminate patients with better survival from patients with short survival. In SCC Multivariate analysis indicated that in our cohort of patients with SCC, better OS and DSS are high expression levels of miR-192. In conclusion, the results obtained by our studies support the possibility of the use of selected miRNAs as prognostic biomarkers in cytologic and histologic clinical samples of lung tumours.