Abstract

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. This complex disease still holds severe problems concerning diagnosis due to the high invasiveness nature of colonoscopy and the low accuracy of the alternative diagnostic methods. Additionally, patient heterogeneity even within the same stage is not properly reflected in the current stratification system. This scenario highlights the need for new biomarkers to improve non-invasive screenings and clinical management of patients.

MicroRNAs (miRNAs) have emerged as good candidate biomarkers in cancer as they are stable molecules, easily measurable and detected in body fluids thus allowing for non-invasive diagnosis and/or prognosis.

In this study, we performed an integrated analysis first using 4 different datasets (discovery cohorts) to identify miRNAs associated with colorectal cancer development, unveil their role in this disease by identifying putative targets and regulatory networks and investigate their ability to serve as biomarkers. We have identified 26 differentially expressed miRNAs which interact with frequently deregulated genes known to participate in commonly altered pathways in colorectal cancer. Most of these miRNAs have high diagnostic power, and their prognostic potential is evidenced by panels of 5 miRNAs able to predict the outcome of stage II and III colorectal cancer patients. Notably, 8 miRNAs were validated in three additional independent cohorts (validation cohorts) including a plasma cohort thus reinforcing the value of miRNAs as non-invasive biomarkers.