A Targeted Proteomics Approach Reveals a Serum Protein Signature as a Diagnostic Biomarker for Colorectal Cancer

Circulating proteins secreted by tumors are an important source of cancer biomarkers. This study aims to investigate the changes in the content of tumor immune-related circulating proteins in peripheral blood from patients with colorectal cancer (CRC).

Olink's proximity extension assay was used to detect the levels of 92 tumor immune-related circulating proteins in peripheral blood from CRC patients. An enzyme-linked immunosorbent assay was performed to detect the levels of six proteins. Elastic network regression was used to establish the model, and the performance of the model was verified by multiple iterations of cross-validation.

The best serum protein signature that was composed of six proteins (IL7, CXCL12, IL10, IL15, CXCL1, and MCP-3) was selected. The area under the curve value of this signature was 0.9924 in the training set and 0.8992 in the total set. IL7 and IL15 levels were significantly higher in the ≥4 cm tumor volume group than in the <4 cm tumor volume group (P = 0.0113 and P = 0.004, respectively). MCP-3 levels were significantly higher in the distant metastasis group than in the non-distant metastasis group (P =0.0465). There was a significant difference in MCP-3 levels among different tumor, node, metastasis stages (P = 0.0496). CXCL1 levels were positively correlated with the absolute count of basophils (R = 0.3220, P = 0.0273), and IL10 levels were positively correlated with the absolute count of neutrophils (R = 0.38737, P = 0.0078). CXCL1, IL7, and IL15 were independent prognostic factors of CRC (hazard ratio [HR] = 0.62, P = 0.006; HR = 0.57, P = 0.006; and HR = 0.64, P = 0.011, respectively).

The best serum protein signature model (IL7, CXCL12, IL10, IL15, CXCL1, and MCP-3) was able to distinguish CRC patients from healthy controls. These proteins were also involved in the occurrence and development of CRC.