Quantitative proteomic analysis reveals functional alterations of the peripheral immune system in colorectal cancer

Wenyuan Zhu; Minzhe Li; Qingsong Wang; Jian Shen; Jianguo Ji

doi:10.1016/j.mcpro.2024.100784

Quantitative proteomic analysis reveals functional alterations of the peripheral immune system in colorectal cancer

Mol Cell Proteomics. 2024 May 10:100784. doi: 10.1016/j.mcpro.2024.100784. Online ahead of print.

Authors

Wenyuan Zhu¹, Minzhe Li², Qingsong Wang³, Jian Shen⁴, Jianguo Ji⁵

Affiliations

¹ State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China; Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing, China.
² General Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
³ State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China; Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing, China. Electronic address: wangqingsong@pku.edu.cn.
⁴ General Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. Electronic address: Shenjian@ccmu.edu.cn.
⁵ State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China; Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing, China. Electronic address: jijg@pku.edu.cn.

PMID: 38735538
DOI: 10.1016/j.mcpro.2024.100784

Abstract

Colorectal cancer (CRC) is characterized by high morbidity, high mortality, and limited response to immunotherapies. The peripheral immune system is an important component of tumor immunity, and enhancements of peripheral immunity help to suppress tumor progression. However, the functional alterations of the peripheral immune system in CRC are unclear. Here, we used mass spectrometry-based quantitative proteomics to establish a protein expression atlas for the peripheral immune system in CRC, including plasma and five types of immune cells (CD4⁺ T cells, CD8⁺ T cells, monocytes, natural killer cells, and B cells). Synthesizing the results of the multidimensional analysis, we observed an enhanced inflammatory phenotype in CRC, including elevated expression of plasma inflammatory proteins, activation of the inflammatory pathway in monocytes, and increased inflammation-related ligand-receptor interactions. Notably, we observed tumor effects on peripheral T cells, including altered cell subpopulation ratios and suppression of cell function. Suppression of CD4⁺ T cell function is mainly mediated by high expression levels of protein tyrosine phosphatases. Among them, the expression of protein tyrosine phosphatase receptor type J (PTPRJ) gradually increased with CRC progression; knockdown of PTPRJ in vitro could promote T cell activation, thereby enhancing peripheral immunity. We also found that the combination of leucine-rich α-2 glycoprotein 1 (LRG1) and apolipoprotein A4 (APOA4) had the best predictive ability for colorectal cancer and has the potential to be a biomarker. Overall, this study provides a comprehensive understanding of the peripheral immune system in CRC. It also offers insights regarding the potential clinical utilities of these peripheral immune characteristics as diagnostic indicators and therapeutic targets.

Keywords: Biomarker; Colorectal cancer; Ligand-receptor interaction; Peripheral immune system; Quantitative proteomics.