CHI3L1 elevation

Despite its therapeutic potential, challenges remain in developing selective and safe CHI3L1-targeted therapies, particularly in ensuring effective delivery across the blood-brain barrier and mitigating off-target effects. This review addresses the complexities of targeting CHI3L1, highlights its potential in precision medicine, and outlines future research directions aimed at unlocking its full therapeutic potential in treating neurodegenerative diseases and brain pathologies.

Comparative analysis with YKL-39, which does not contain a corresponding W69 residue, highlights the unique role of this residue in YKL-40's chitin-binding activity that is potentially linked to immune and inflammatory responses. Our evaluation method clarifies YKL-40's binding properties and provides a versatile approach applicable to other chitin-binding proteins.

This study found that the YKL-40 expression level was significantly stronger in low-grade than in high-grade canine cutaneous mast cell tumors and was associated with various clinical and pathological features. Stronger YKL-40 expression level correlated with longer survival time, especially in low-grade cMCTs. Therefore, YKL-40 could serve as a prognostic marker for cMCTs.

Our results confirmed that the CHI3L1 could serve as an independent predictor for OS in HCC patients after hepatectomy. The nomogram showed a good performance in prognosis prediction of HCC.

Regarding the prognostic capability, YKL-40 ≥100 ng/ml (the median cut-off value) (P = 0.003) and YKL-40 ≥150 ng/ml (the third interquartile cut-off value) (P = 0.021) reflected an elevated accumulating MACE rate, whereas accumulating MACE was not different between CHD patients with YKL-40 ≥80 and <80 ng/ml (the first interquartile cut-off value) (P = 0.083). Serum YKL-40 is positively linked with inflammatory cytokines and the Gensini score, whose high expression cut-off by 100 and 150 ng/ml estimates a higher MACE risk in CHD patients.

Elevated CHI3L1 expression was associated with genes which were related to the recruitment and infiltration of neutrophils. Consequently, CHI3L1 may serve as a novel evaluation factor for the degree of neutrophil infiltration in advanced bladder cancer in those scheduled for chemotherapy.

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.

Six independent cohorts of CRC patients were stratified by YKL-40 tissue expression to define its prognostic role and its effect on cetuximab and oxaliplatin treatment response. YKL-40 high-expressing HCT116 and Caco2 cells showed increased motility, invasion and proliferation. Our study recognizes a novel role of YKL-40 tissue expression in promoting CRC metastatic potential, through EMT signaling activation, and provides significant clinical implications that may impact the risk prediction of patients with mCRC. YKL-40 high tissue levels also strengthen a predictive value for better cetuximab responsiveness, even in patients with KRAS mutations. Since resistance to cetuximab remains one of the greatest challenges in treating CRC, our findings may be crucial for developing novel YKL-40-targeted therapy approaches.

CHI3L1 level in CSF is correlated with the severity and prognosis of anti-LGI1 encephalitis. (CSF CHI3L1 levels are correlated with the severity and prognosis of anti-LGI1 encephalitis.).

Strikingly, high YKL-40 tissue levels showed a predictive value for a better response to cetuximab, even in patients with stage IV CRC and mutant KRAS, and worse sensitivity to oxaliplatin. Taken together, our findings establish that tissue YKL-40 overexpression enhances CRC metastatic potential, highlighting this gene as a novel prognostic candidate, a predictive biomarker for therapy response, and an attractive target for future therapy in CRC.

The observed effect of COS could be due to the blocking of YKL-40-receptor binding inhibiting cancer-promoting signaling pathways. Alternative biological functions of COS could also be involved.