Wang L, Wu Q, Zhang ZW, Zhang H, Jin H, Zhou XL, Liu JY, Li D, Liu Y, Fan ZS. Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric cancer. World J Gastrointest Oncol 2025; 17(2): 97858 [PMID: 39958563 DOI: 10.4251/wjgo.v17.i2.97858]
Corresponding Author of This Article
Zhi-Song Fan, Associate Chief Physician, Associate Professor, MD, PhD, Department of Oncology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang 050011, Hebei Province, China. fanzs@hebmu.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Feb 15, 2025; 17(2): 97858 Published online Feb 15, 2025. doi: 10.4251/wjgo.v17.i2.97858
Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric cancer
Long Wang, Qi Wu, Zong-Wen Zhang, Hui Zhang, Hui Jin, Xin-Liang Zhou, Jia-Yin Liu, Dan Li, Yan Liu, Zhi-Song Fan
Long Wang, Qi Wu, Zong-Wen Zhang, Hui Zhang, Hui Jin, Xin-Liang Zhou, Jia-Yin Liu, Dan Li, Yan Liu, Zhi-Song Fan, Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Co-first authors: Long Wang and Qi Wu.
Author contributions: Wang L and Wu Q contributed equally to this article, they are the co-first authors of this manuscript; Fan ZS designed the research study; Fan ZS, Wu Q, and Wang L carried out the entire research; Fan ZS, Wu Q, and Wang L wrote the article; Zhang ZW conducted bioinformatics analysis; Zhang H and Jin H provided guidance and revised the manuscript; Zhou XL, Liu JY, and Li D contributed to the experimental research; and all authors have read and approved the final manuscript.
Supported by Hebei Province Medical Science Research Project Plan, No. 20230755.
Institutional review board statement: The study was reviewed and approved by the Fourth Hospital of Hebei Medical University Institutional Review Board, approval No. 2022KY247.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhi-Song Fan, Associate Chief Physician, Associate Professor, MD, PhD, Department of Oncology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang 050011, Hebei Province, China. fanzs@hebmu.edu.cn
Received: June 11, 2024 Revised: October 29, 2024 Accepted: November 8, 2024 Published online: February 15, 2025 Processing time: 221 Days and 0.4 Hours
Abstract
BACKGROUND
Colony-stimulating factor 3 (CSF3) and its receptor (CSF3R) are known to promote gastric cancer (GC) growth and metastasis. However, their effects on the immune microenvironment remain unclear. Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2 (LILRB2) in GC. We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands, angiopoietin-like protein 2 (ANGPTL2) and human leukocyte antigen-G (HLA-G), contributing to immunosuppression.
AIM
To investigate the relationship between CSF3/CSF3R and LILRB2, as well as its ligands ANGPTL2 and HLA-G, in GC.
METHODS
Transcriptome sequencing data from The Cancer Genome Atlas were analyzed, stratifying patients by CSF3R expression. Differentially expressed genes and immune checkpoints were evaluated. Immunohistochemistry (IHC) was performed on GC tissues. Correlation analyses of CSF3R, LILRB2, ANGPTL2, and HLA-G were conducted using The Cancer Genome Atlas data and IHC results. GC cells were treated with CSF3, and expression levels of LILRB2, ANGPTL2, and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.
RESULTS
Among 122 upregulated genes in high CSF3R expression groups, LILRB2 showed the most significant increase. IHC results indicated high expression of LILRB2 (63.0%), ANGPTL2 (56.5%), and HLA-G (73.9%) in GC tissues. Strong positive correlations existed between CSF3R and LILRB2, ANGPTL2, and HLA-G mRNA levels (P < 0.001). IHC confirmed positive correlations between CSF3R and LILRB2 (P < 0.001), and HLA-G (P = 0.010), but not ANGPTL2 (P > 0.05). CSF3 increased LILRB2, ANGPTL2, and HLA-G expression in GC cells. Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression, impacting CSF3’s regulatory effects.
CONCLUSION
The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands, with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.
Core Tip: This study investigates the relationship between colony-stimulating factor 3 (CSF3)/colony-stimulating factor 3 receptor (CSF3R) and leukocyte immunoglobulin-like receptor B2, along with its ligands angiopoietin-like protein 2 and human leukocyte antigen-G, in gastric cancer (GC). High CSF3R expression correlates with increased levels of leukocyte immunoglobulin-like receptor B2, along with its ligands angiopoietin-like protein 2, and human leukocyte antigen-G in both transcriptomic data and immunohistochemical analysis. CSF3 upregulates these immune checkpoints in GC cells, with heterogeneous nuclear ribonucleoprotein H1 modulating this effect. These findings suggest that the CSF3/CSF3R pathway may play a role in promoting immunosuppression in GC.
