Increased blood microRNA-320 expression associated with imminent and severe lung cancer

Altered levels of microRNAs (miRNAs) in blood may contribute to identification of individuals with lung cancer (LC) but may also be early systemic signals of increased LC risk. We compared expression of 1663 miRNAs in blood collected during diagnostic workup for confirmed LC cases (n=128) to that in individuals with suspected but confirmed negative LC (n=62) and identified nine candidate miRNAs upregulated in LC cases. Higher expression of three candidates, miR-320b, 320c, and 320d, was associated with poor survival, independent of LC stage and subtype. To investigate pre-diagnostic profiles of the candidate miRNAs, we assessed their blood expression up to eight years prior to LC diagnosis in population-based cohorts compared to matched controls (n=360 cases, 375 controls). Expression of miR-320c and miR-320d was higher especially in cases sampled within two years prior to LC diagnosis. Thus, elevated levels of miR-320c and miR-320d may be early indications of severe LC. MicroRNA expression profiles from small RNA sequencing of serum from lung cancer patients at diagnosis (n=128) and individuals with confirmed negative LC (n=62). **Raw data not provided due to patient privacy concerns**