Early Onset Colorectal Cancer Detection

The rising incidence of early-onset colorectal cancer (EOCRC) is a pressing clinical issue unique to our times, and it is expected to grow with an anticipated further 90% increase in incidence by the decade's end. Challenges persist even after reducing the CRC screening age to 45: under-45s lack routine screening and compliance in the 45-50 age group remains low, partly due to invasiveness and discomfort of standard screening methods. Urgent action is warranted to develop affordable, sensitive, and feasible screening for timely detection and improved participation. A non-invasive, patient-friendly screening test, like a blood-based assay, could address these epidemiological concerns and also attract underserved populations. This study involves the development and validation of a liquid biopsy, assessing circulating cell-free and exosomal microRNAs (cf-miRNA and exo-miRNA, respectively) for indirect sampling of tumor tissue in the bloodstream. The researchers intend to harness machine learning and bioinformatics to create an integrated panel (with both cf-miRNAs and exo-miRNAs) to enhance the inherently high sensitivity of cf-miRNAs with the distinctive specificity of exo-miRNAs. This combined approach will not only improve the performance of a diagnostic model but will also tap into the diverse tumor biology aspects of EOCRC. The study's core goal is to develop cost-efficient, non-invasive, clinic-friendly biomarkers with high sensitivity and specificity, aiding EOCRC detection. The researchers intend to do so in three phases: 1. To perform comprehensive small RNA-Seq from matched cf-miRNA, exo-miRNA, cancer-derived miRNA, and mucosa-derived miRNA. 2. To develop and train two miRNA detection panels (cf-miRNA and exo-miRNA, respectively) based on advanced machine-learning models and, then, combine these two using several machine-learning models to obtain a final detection biomarker. 3. To validate the findings in an independent cohort of EOCRC and controls. In summary, this proposal promises to improve patient care and compliance, and, ultimately, reduce mortality from EOCRC.