Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, driven largely by pronounced molecular heterogeneity and delayed clinical detection. Although high-throughput sequencing technologies have substantially advanced the understanding of CRC biology, their routine clinical implementation remains constrained by high costs, infrastructural requirements, and limited accessibility. This review addresses these translational barriers by systematically synthesizing circulating transcriptomic and proteomic biomarkers within a clinically scalable framework. Particular emphasis is placed on biomolecules detectable using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), two widely accessible platforms that underwent extensive global optimization during the COVID-19 pandemic and are readily adaptable to liquid biopsy workflows. Through a stage-resolved analysis, we identify 9 genomic and 7 proteomic biomarkers associated with early-stage (I-II) CRC, alongside 9 genomic and 4 proteomic biomarkers linked to advanced-stage (III-IV) disease progression. Beyond biomarker cataloging, these molecules are integrated with Cancer Hallmark pathways, clinical-stage associations, and available clinical trial evidence to evaluate their biological relevance and translational readiness. In addition, we summarize standardized operating procedure (SOP) considerations and multiplex detection strategies to improve assay reproducibility, scalability, and cross-border clinical implementation. Collectively, this review bridges molecular discovery with clinically deployable laboratory workflows and provides a translational roadmap for the development of affordable, liquid biopsy-based diagnostic strategies aimed at improving CRC detection, patient stratification, longitudinal monitoring, and early therapeutic intervention.
Raajesh Anand (Mon,) studied this question.