Abstract

Colorectal cancer (CRC) remains a major global health burden, necessitating more effective and targeted screening 
strategies. Proteogenomics, which integrates genomic, transcriptomic, and proteomic data, has emerged as a 
promising approach for improving CRC risk stratification, early detection, and therapeutic decision-making. This 
study examines the clinical validity and utility of proteogenomics in CRC, with a focus on its implications for 
population screening and health policy. Current evidence demonstrates that while proteogenomic profiling 
enhances understanding of tumor biology, genotype–phenotype associations, and disease progression, its clinical 
validity for widespread screening remains insufficient. Nonetheless, proteogenomics shows potential in identifying 
high-risk individuals, refining screening paradigms, and supporting precision medicine approaches. The review 
further highlights key challenges, including limited reproducibility, lack of standardized methodologies, 
insufficient longitudinal and health-economic data, and regulatory uncertainties. Importantly, issues of equity, 
access, and infrastructure readiness must be addressed before large-scale implementation. Lessons from existing 
CRC research emphasize the need for robust validation studies, standardized reporting frameworks, and 
integration with existing screening tools such as fecal immunochemical testing (FIT) and colonoscopy. Overall, 
while proteogenomics offers significant promise for transforming CRC screening and management, its translation 
into population-level programs requires further evidence, interdisciplinary collaboration, and policy development. 
Future research should prioritize clinical validation, cost-effectiveness analysis, and equitable implementation 
strategies to ensure that the benefits of proteogenomics are both clinically meaningful and socially inclusive.