Ubiquitinomics in Sigmoid Colon Cancer: Defining Stage-Specific Patterns for Predictive, Preventive, and Personalized Medicine

Sigmoid colon cancer (SCC) is a distinct clinical and molecular subtype of colorectal cancer, characterized by unique molecular, diagnostic, therapeutic, and prognostic features. Recent ubiquitinomics profiling identified 608 differentially ubiquitinated proteins (DUPs) with 1249 ubiquitinated sites, revealing stage-specific patterns. Early stages exhibit ubiquitination changes facilitating oncogenic evasion, while advanced stages show DUPs driving metastasis, therapy resistance, and immune evasion. Key pathways include Salmonella infection, ferroptosis, and glycolysis. Crucially, 46 survival-associated DUPs serve as prognostic biomarkers and therapeutic targets. Despite these advances, clinical translation faces limitations, including technical challenges in ubiquitinomics such as inability to resolve polyubiquitin chain topology, biological heterogeneity, subsite generalization, and validation gaps. Future efforts require refined ubiquitin detection methods, functional validation of DUPs, multi-omic integration, and prospective clinical studies. Overcoming these barriers will enable predictive diagnostics, preventive strategies like targeting pre-malignant ubiquitination, and personalized therapies such as DUB inhibitors, PROTACs, advancing the predictive, preventive, personalized medicine (3 PM) framework for SCC management.