Proteomic screening of potential N-glycoprotein biomarkers for colorectal cancer by TMT labeling combined with LC-MS/MS

Background and aims: Colorectal cancer (CRC) is part of the most widespread malignant tumors. At present, colonoscopy is a routine procedure in the diagnosis of CRC, but it is traumatic. Carcinoembryonic antigen, CA199, and CA242 are common serum markers for the diagnosis of CRC; however, they do not demonstrate satisfactory specificity and sensitivity for the diagnosis of CRC. Hence, Now it is necessary to screen many valuable serum biomarkers for CRC, proteomics methods have been used to investigate PTMs such as glycosylation of proteins with prominent roles in the occurrence and development of tumors. Methods: This study screens altering glycosylated proteins of CRC tissues using LC-MS/MS quantitative glycoproteomics, and then these candidate biomarkers for CRC are further validated by serum glycoproteomics. Results: The results of glycoproteomics in CRC tissues show that the abundance of 160 and 79 glycerogelatin proteins was obviously upregulated and downregulated compared with their adjacent tissues(P < 0.05). Bioinformatics analysis suggests that these molecules are mainly involved in many biological processes, including skeletal system development, collagen fibril organization, and receptor-mediated endocytosis. Results of serum glycoproteomics show that the changing trends of 2 protein glycosylation were consistent with MS results of CRC tissues, including ICAM1and APMAP. Areas under the ROC curve (AUC) results confirm that ICAM1and APMAP as early immune diagnosis markers of CRC has excellent sensitivity and specificity. Conclusion: The ICAM1 and APMAP may serve as a potential tumor marker for CRC.

Automated summary

This study identified potential tumor markers for CRC through quantitative glycoproteomics analysis of CRC tissues and serum samples. Results indicate that ICAM1 and APMAP show promise as early immune diagnosis markers for CRC with excellent sensitivity and specificity. Ultimately, these findings suggest the potential use of ICAM1 and APMAP as valuable biomarkers for colorectal cancer.