CHI3L2 Is a Novel Prognostic Biomarker and Correlated With Immune Infiltrates in Gliomas

Liling Liu; Yuanzhong Yang; Hao Duan; Jiahua He; Lu Sun; Wanming Hu; Jing Zeng

doi:10.3389/fonc.2021.611038

CHI3L2 Is a Novel Prognostic Biomarker and Correlated With Immune Infiltrates in Gliomas

Front Oncol. 2021 Apr 15:11:611038. doi: 10.3389/fonc.2021.611038. eCollection 2021.

Authors

Liling Liu^{1

2}, Yuanzhong Yang^{1

2}, Hao Duan^{2

3}, Jiahua He^{1

2}, Lu Sun^{1

2}, Wanming Hu^{1

2}, Jing Zeng^{1

2}

Affiliations

¹ Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
² State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
³ Department of Neurosurgery, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Abstract

CHI3L2 (Chitinase-3-Like Protein 2) is a member of chitinase-like proteins (CLPs), which belong to the glycoside hydrolase 18 family. Its homologous gene, CHI3L1, has been extensively studied in various tumors and has been shown to be related to immune infiltration in breast cancer and glioblastoma. High CHI3L2 expression was reported to be associated with poor prognosis in breast cancer and renal cell carcinoma. However, the prognostic significance of CHI3L2 in glioma and its correlation between immune infiltration remains unclear. In this study, we examined 288 glioma samples by immunohistochemistry to find that CHI3L2 is expressed in tumor cells and macrophages in glioma tissues and highly expressed in glioblastoma and IDH wild-type gliomas. Relationships between CHI3L2 expression and clinical features (grade, age, Ki67 index, P53, PHH3 (mitotic figures), ATRX, TERTp, MGMTp, IDH, and 1p/19q co-deleted status) were evaluated. Kaplan-Meier survival was conducted to show high CHI3L2 expression in tumor cells (TC) and macrophage cells (MC) indicated poor prognosis in diffusely infiltrating glioma (DIG), lower-grade glioma (LGG), and IDH wild-type gliomas (IDH-wt). The overall survival time was higher in patients with dual-low CHI3L2 expression in TC and MC compared to those in patients with non-dual CHI3L2 expression and dual high expression in DIG and IDH wild-type gliomas. By univariate and multivariate analysis, we found that high CHI3L2 expression in tumor cells was an independent unfavorable prognostic factor in glioma patients. Moreover, we used two datasets (TCGA and CGGA) to verify the results of our study and explore the potential functional role of CHI3L2 by GO and KEGG analyses in gliomas. TIMER platform analysis indicated CHI3L2 expression was closely related to diverse marker genes of tumor immune infiltrating cells, including monocytes, TAMs, M1 macrophages, M2 macrophages, TGFβ1+ Treg and T cell exhaustion in GBM and LGG. Western Blot validated CHI3L2 is expressed in glioma cells and microglia cells. The results of flow cytometry showed that CHI3L2 induces the apoptosis of CD8+ T cells. In conclusion, these results demonstrate CHI3L2 is related to poor prognosis and immune infiltrates in gliomas, suggesting it may serve as a promising prognostic biomarker and represent a new target for glioma patients.

Keywords: CGGA; CHI3L2; TCGA; gliomas; immune infiltrates; prognosis.