Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas

Jinchao Wang; Linzong Xu; Qian Ding; Xiaoru Li; Kai Wang; Shangchen Xu; Bin Liu

doi:10.3389/fimmu.2023.1065062

Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas

Front Immunol. 2023 May 30:14:1065062. doi: 10.3389/fimmu.2023.1065062. eCollection 2023.

Authors

Jinchao Wang^{1

2}, Linzong Xu³, Qian Ding⁴, Xiaoru Li^{1

2}, Kai Wang^{1

2}, Shangchen Xu¹, Bin Liu⁵

Affiliations

¹ Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, China.
² Graduate School of Medicine, Shandong First Medical University, Jinan, China.
³ Tumor Research and Therapy Center, Shandong Provincial Hospital, Shandong University, Jinan, China.
⁴ Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, China.
⁵ Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, China.

Abstract

Background: Siglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods.

Methods: The bioinformatics approach was used to examine Siglec15 mRNA expression in gliomas based on TCGA, CGGA, and GEO datasets. Then, the predictive value of Siglec15 expression on progression-free survival time (PFST) and overall survival time (OST) in glioma patients was comprehensively described.The TCGA database was screened for differentially expressed genes (DEGs) between the high and low Siglec15 expression groups, and enrichment analysis of the DEGs was performed. The Siglec15 protein expression and its prognostic impact in 92 glioma samples were explored using immunohistochemistry Next, the relationships between Siglec15 expression and infiltrating immune cells, immune regulators and multiple immune checkpoints were analysed.

Results: Bioinformatics analyses showed that high Siglec15 levels predicted poor clinical prognosis and adverse recurrence time in glioma patients. In the immunohistochemical study serving as a validation set, Siglec15 protein overexpression was found in 33.3% (10/30) of WHO grade II, 56% (14/25) of WHO grade III, and 70.3% (26/37) of WHO grade IV gliomas respectively. Siglec15 protein overexpression was also found to be an independent prognostic indicator detrimental to the PFST and OST of glioma patients. Enrichment analysis showed that the DEGs were mainly involved in pathways associated with immune function, including leukocyte transendothelial migration, focal adhesion, ECM receptor interaction, and T-cell receptor signaling pathways. In addition, high Siglec15 expression was related to M2 tumor-associated macrophages (TAMs), N2 tumor-infiltrating neutrophils, suppressive tumor immune microenvironment, and multiple immune checkpoint molecules. Immunofluorescence analysis confirmed the colocalization of Siglec15 and CD163 on TAMs.

Conclusion: Siglec15 overexpression is common in gliomas and predicts an adverse recurrence time and overall survival time. Siglec15 is a potential target for immunotherapy and a potential TAMs regulator that is involved in the suppressed immunomicroenvironment in gliomas.

Keywords: SIGLEC15; gliomas; immune checkpoint; macrophages; prognostic indicator.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Glioma* / genetics
Humans
Macrophages
Pancreatic Neoplasms*
Prognosis
Tumor Microenvironment / genetics
Tumor-Associated Macrophages

Substances

SIGLEC15 protein, human

Grants and funding

This study was supported by National Natural Science Foundation of China (no. 81902531 and 82000566) and Shandong Provincial Natural Science Foundation (grant numbers ZR2020QH036).