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Objective <p>This study aims to investigate the expression of Chitinase-3-like protein-1 (CHI3L1) in gastric cancer (GC) tissues and serum from patients, analyze the correlation between CHI3L1 expression and GC patients’ clinicopathological parameters, evaluate its impact on patient prognosis and the tumor immune microenvironment, and explore the potential of CHI3L1 as a diagnostic biomarker in GC.</p> Materials and methods <p>The expression of CHI3L1 in GC was investigated using data from The Cancer Genome Atlas (TCGA) and TIMER databases. The association between CHI3L1 expression and prognosis in GC patients was analyzed through the TCGA database. Serum samples were collected from 87 patients with GC, 38 patients with gastric precancerous lesions, and 42 healthy volunteers. The levels of CHI3L1 in serum specimens were measured via chemiluminescent immunoassay (CLIA), and the receiver operating characteristic (ROC) curve was employed to further evaluate the diagnostic efficacy of CHI3L1. Gene Set Enrichment Analysis (GSEA) was performed using gene sets from the Molecular Signatures Database (MsigDB). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on correlated genes obtained from the LinkedOmics database. Additionally, the CIBERSORT algorithm was applied to investigate the correlation between CHI3L1 and gastric cancer immune infiltration, aiming to explore the potential mechanisms of CHI3L1 in GC.</p> Results <p>CHI3L1 expression was significantly upregulated in GC (<i>P</i> &lt; 0.05) and exhibited strong correlations with GC subtypes, tumor differentiation grade, primary tumor status, regional lymph node metastasis, distant metastasis, clinical stage, Borrmann classification, and tumor size (all <i>P</i> &lt; 0.05). Prognostic analysis revealed correlations between patient survival and age, primary tumor status, regional lymph node metastasis, distant metastasis, clinical stage, new tumor events, and residual tumor (all <i>P</i> &lt; 0.05). Notably, CHI3L1 demonstrated high diagnostic efficacy for GC (In the TCGA database: AUC = 0.861, <i>P</i> &lt; 0.0001; For the serum samples: AUC = 0.932, <i>P</i> &lt; 0.0001). Gene Set Enrichment Analysis (GSEA) suggested that CHI3L1 is involved in multiple oncogenic signaling pathways, including the NF-κB, IL-17, and ECM-receptor interaction pathways. Functional enrichment analysis further linked CHI3L1 to inflammatory response and immune regulation, while immune infiltration analysis via CIBERSORT indicated significant correlations between CHI3L1 expression and infiltration levels of multiple immune cell types.</p> Conclusions <p>CHI3L1, an oncogenic glycoprotein, is highly expressed in GC and involved in immune infiltration, holding promise as a diagnostic biomarker for GC.</p>

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CHI3L1 is a diagnostic biomarker involved in immune infiltration of gastric cancer

  • 期刊论文

  • 发表日期：

    2025年10月16日

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  • Yongkang Yan,
  • Wei Li,
  • Huifang Liu,
  • Hui Zhao,
  • Jing Li,
  • Tongtong Wang,
  • Zhiwei Tian,
  • Jie Yang

摘要

Objective

This study aims to investigate the expression of Chitinase-3-like protein-1 (CHI3L1) in gastric cancer (GC) tissues and serum from patients, analyze the correlation between CHI3L1 expression and GC patients’ clinicopathological parameters, evaluate its impact on patient prognosis and the tumor immune microenvironment, and explore the potential of CHI3L1 as a diagnostic biomarker in GC.

Materials and methods

The expression of CHI3L1 in GC was investigated using data from The Cancer Genome Atlas (TCGA) and TIMER databases. The association between CHI3L1 expression and prognosis in GC patients was analyzed through the TCGA database. Serum samples were collected from 87 patients with GC, 38 patients with gastric precancerous lesions, and 42 healthy volunteers. The levels of CHI3L1 in serum specimens were measured via chemiluminescent immunoassay (CLIA), and the receiver operating characteristic (ROC) curve was employed to further evaluate the diagnostic efficacy of CHI3L1. Gene Set Enrichment Analysis (GSEA) was performed using gene sets from the Molecular Signatures Database (MsigDB). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on correlated genes obtained from the LinkedOmics database. Additionally, the CIBERSORT algorithm was applied to investigate the correlation between CHI3L1 and gastric cancer immune infiltration, aiming to explore the potential mechanisms of CHI3L1 in GC.

Results

CHI3L1 expression was significantly upregulated in GC (P < 0.05) and exhibited strong correlations with GC subtypes, tumor differentiation grade, primary tumor status, regional lymph node metastasis, distant metastasis, clinical stage, Borrmann classification, and tumor size (all P < 0.05). Prognostic analysis revealed correlations between patient survival and age, primary tumor status, regional lymph node metastasis, distant metastasis, clinical stage, new tumor events, and residual tumor (all P < 0.05). Notably, CHI3L1 demonstrated high diagnostic efficacy for GC (In the TCGA database: AUC = 0.861, P < 0.0001; For the serum samples: AUC = 0.932, P < 0.0001). Gene Set Enrichment Analysis (GSEA) suggested that CHI3L1 is involved in multiple oncogenic signaling pathways, including the NF-κB, IL-17, and ECM-receptor interaction pathways. Functional enrichment analysis further linked CHI3L1 to inflammatory response and immune regulation, while immune infiltration analysis via CIBERSORT indicated significant correlations between CHI3L1 expression and infiltration levels of multiple immune cell types.

Conclusions

CHI3L1, an oncogenic glycoprotein, is highly expressed in GC and involved in immune infiltration, holding promise as a diagnostic biomarker for GC.