Do Elevated YKL-40 Levels Drive the Immunosuppressive Tumor Microenvironment in Colorectal Cancer? Assessment of the Association of the Expression of YKL-40, MMP-8, IL17A, and PD-L1 with Coexisting Type 2 Diabetes, Obesity, and Active Smoking

Abstract

The influence of chitinase-3-like protein 1 (YKL-40 or CHI3L1) expression on the immunological properties of the tumor microenvironment, which may affect the effectiveness of immunotherapy, is currently not sufficiently understood in colorectal cancer (CRC). The aim of this study was to investigate the relationship between YKL-40 expression and the immunological properties of the tumor microenvironment in CRC. We performed in silico analysis, including analysis of immune cell infiltration scores and the immune landscape depending on YKL-40 expression, gene set enrichment analysis (GSEA), and analysis of three Gene Expression Omnibus (GEO) datasets. In 48 CRC tissue homogenates and the surgical margin, we analyzed the expression of YKL-40, MMP8, IL17A, and PD-L1. Moreover, we analyzed the expression of YKL-40 in tissue homogenates retrieved from patients with coexisting diabetes, obesity, and smoking. The expression of YKL-40 was significantly higher in CRC tumor tissue compared to healthy tissue and correlated with MMP-8, IL17A, and PD-L1 expression. In silico analysis revealed an association of YKL-40 with disease recurrence, and GSEA revealed a potential link between elevated YKL-40 expression and immunosuppressive properties of the tumor microenvironment in CRC.

Association study for the role of MMP8 gene polymorphisms in Colorectal cancer susceptibility

“…Protein array analysis showed decreased levels of circulating angiogenesis factor MMP8 during treatment with bevacizumab in metastatic CRC [ 24 ]. In CRC tissues, YKL-40 is associated with the expression of MMP8 and may be involved in the immunological properties of the tumor microenvironment [ 25 ]. MMP8.…”

Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases

“…CHI3L1 is upregulated in CRC progression and plays a significant role in promoting macrophage infiltration, angiogenesis, and the secretion of IL-8 and MCP-1 [34]. In CRC tumor tissue, CHI3L1 is associated with the expression of MMP-8, IL17A, and PD-L1, thereby influencing the tumor microenvironment [168]. Kawada et al discovered that CHI3L1 in CRC patients primarily originates from human colorectal cancer cells rather than inflammatory cells.…”