CHI3L1 (Chitinase 3 Like 1) upregulation is associated with macrophage signatures in esophageal cancer

ABSTRACT

Chitinase-3 like-protein-1 (CHI3L1) has been found to be overexpressed in many cancers and increased CHI3L1 level in serum seems to correlate with a poor prognosis in patients with metastatic cancer. However, the expression of CHI3L1 and its potential role in esophageal cancer remains unclear. We retrieved publicly available RNA-seq datasets of esophageal cancer tissues and normal esophageal tissues. We analyzed the correlation between CHI3L1 expression with different clinical parameters (such as T stages, N stage, response to treatment and tumor residues after treatment), the relationship between CHI3L1 expression level and prognosis, and the relationship between CHI3L1 expression and different immune cell signatures in esophageal cancer tissues. A transgenic mouse model of esophageal carcinoma was used to validate CHI3L1 expression and its association with macrophage signature gene expression. The effect of recombinant CHI3L1 on macrophage polarization was assessed in cell model. We showed the upregulation of CHI3L1 in esophageal cancer tissues in comparison to normal esophageal tissues, and its upregulation was positively associated with tumor size. The analysis of immunological signatures and CHI3L1 expression indicated that CHI3L1 level was highly correlated with increased expression of macrophage signature genes in esophageal tumor tissues. CHI3L1 was also upregulated in the esophagus dysplasia tissues in a transgenic mouse model. Recombinant CHI3L1 treatment favored M2 gene expression in LPS-stimulated RAW 264.7 macrophage cell line. CHI3L1 overexpression may favor macrophage recruitment in esophageal tumor tissues. Future studies are needed to delineate the mechanisms of CHI3L1-mediated macrophage recruitment and polarization in tumor tissues.

KEYWORDS:

• Esophageal cancer
• CHI3L1
• macrophage
• M2 polarization
• tumor microenvironment (TME)

Highlights

• Chitinase-3 like-protein-1 (CHI3L1) is upregulated in esophagus cancers;

• CHI3L1 upregulation is correlated with macrophage signature genes;

• CHI3L1 is upregulated in esophagus dysplasia tissues in a transgenic mouse model;

• Recombinant CHI3L1 treatment regulates macrophage polarization gene expression.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Guarantor of integrity of the entire study: Weiguo Zhu, Wanwei Wang; Study concepts: Jing Huang, Zhenlin Gu; study design: Jing Huang, Zhenlin Gu; Definition of intellectual content: Jing Huang, Zhenlin Gu; Literature research: Weiguo Zhu, Wanwei Wang; Clinical studies: Jing Huang, Zhenlin Gu, Yingying Xu; Experimental studies: Jing Huang, Zhenlin Gu; Data acquisition: Jing Huang, Zhenlin Gu, Yingying Xu; Statistical analysis: Jing Huang, Zhenlin Gu; Manuscript preparation: Jing Huang, Zhenlin Gu, Lei Jiang; Manuscript editing: Jing Huang, Zhenlin Gu, Wanwei Wang; Manuscript review: Jing Huang, Zhenlin Gu, Weiguo Zhu.

Additional information

Funding

This work was supported by Huai’an Natural Science Research Plan [HAB202026] and the Science Development Fund of Nanjing Medical University [NMUB2020153].