miR122 and miR21 are stable components of miRNA signatures of early lung cancer after validation in three independent cohorts

: Several panels of circulating miRNAs have been reported as potential biomarkers of early lung cancer, yet the overlap of components between different panels is limited and the universality of proposed biomarkers has been minimal across proposed panels. To assess the stability of the diagnostic potential of plasma miRNA signature of early lung cancer among different cohorts, a panel of 24 miRNAs tested in the frame of one lung cancer screening study (MOLTEST-2013, Poland) was validated with material collected in the frame of two other screening studies (MOLTEST-BIS, Poland and SMAC, Italy) using the same standardized analytical platform (the miRCURY LNA miRNA PCR Assay). The analysis of selected miRNAs revealed that two miRs associated with lung cancer development, miR-122 and miR-21, repetitively differentiated healthy participants of the screening and individuals with lung cancer. Additionally, miR-144 differentiated controls and cases specifically in sub-cohorts of adenocarcinomas. Other tested miRNAs did not overlap in the three cohorts. Moreover, classification models based on neither a single miRNA nor multicomponent miRNA panels (24-mer and 7-mer) showed sufficient classification performance required for a standalone diagnostic biomarker (AUC=0.75, AUC=0.70, and AUC=0.53 in MOLTEST-2013, SMAC, and MOLTEST-BIS, respectively, for 7-mer model). Furthermore, the performance of classification in the MOLTEST-BIS cohort with the lowest contribution of adenocarcinomas increased when only this cancer type was considered (AUC=0.60 for 7-mer).