Proteome profiling reveals early diagnostic biomarker candidates for colorectal cancer

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Advanced CRC has a grim prognosis, so there is a high demand for an early non-invasive diagnostic biomarker. METHODS: We present a colorectal tissue-serum proteomics approach combined with external database analysis to identify early diagnostic biomarkers specific to CRC. Subsequently, RT-qPCR, PRM, and ELISA experiments were employed to validate the biomarkers in an independent CRC case-control group. Furthermore, in vitro experiments were conducted to investigate the implications of a biomarker on CRC cell phenotyping. RESULTS: Nine proteins (CA1, HBD, SMPDL3A, HBB, ALAD, S100A4, RAB27B, HBA2, CAT) were identified as potential diagnostic biomarkers. Among them, CA1 and SMPDL3A exhibited CRC specificity. The combination of CA1 and SMPDL3A demonstrated superior diagnostic efficacy in CRC (AUC = 0.917; 95% CI = 0.877-0.957). The overexpression of SMPDL3A inhibits the migration and invasion of CRC cells. CONCLUSIONS: CA1 and SMPDL3A proteins are promising novel specific biomarkers for the early diagnosis of CRC. However, larger prospective trials are necessary to validate their clinical utility.