A proteomics-based approach for serum biomarker discovery in colorectal cancer

Abstract

Colorectal cancer (CRC) continues to pose a significant global health challenge , highlighting the urgent need for robust, reliable, and non-invasive biomarkers for early diagnosis and disease monitoring. In this study, we applied an advanced serum proteomics strategy combining label-free mass spectrometry with targeted multiple reaction monitoring (MRM) to identify candidate biomarkers and therapeutic targets . Analysis of 82 selected serum proteins from healthy controls and CRC patients revealed differential expression of 36 proteins, including 9 upregulated and 27 downregulated in CRC. Pathway analyses indicated suppression of complement and apolipoprotein systems alongside activation of coagulation and extracellular matrix (ECM)-related pathways. Focusing on the complement and apolipoprotein networks, 20 proteins showed significant dysregulation in CRC patients. Receiver operating characteristic (ROC) curve analysis singled out JUP, VTN, APOA4, and C4BPB as promising diagnostic markers, which were subsequently evaluated functionally. These results reveal a complex interplay among immune suppression, metabolic shifts, and ECM remodeling during CRC progression and introduce novel serum protein markers with potential clinical utility for early detection and therapeutic stratification. Collectively, this study identifies serum protein signatures that not only discriminate CRC patients from healthy individuals but also contribute mechanistically to tumor advancement, supporting their future use in precision oncology diagnostics and therapy.