集落刺激因子3及其受体促进胃癌中白细胞免疫球蛋白样受体B2的表达及配体。
Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric cancer.
作者信息
Wang Long, Wu Qi, Zhang Zong-Wen, Zhang Hui, Jin Hui, Zhou Xin-Liang, Liu Jia-Yin, Li Dan, Liu Yan, Fan Zhi-Song
机构信息
Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China.
出版信息
World J Gastrointest Oncol. 2025 Feb 15;17(2):97858. doi: 10.4251/wjgo.v17.i2.97858.
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 ( < 0.001). IHC confirmed positive correlations between CSF3R and LILRB2 ( < 0.001), and HLA-G ( = 0.010), but not ANGPTL2 ( > 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.
背景
已知集落刺激因子3（CSF3）及其受体（CSF3R）可促进胃癌（GC）的生长和转移。然而，它们对免疫微环境的影响仍不清楚。我们的分析表明，GC中CSF3R表达与免疫抑制受体白细胞免疫球蛋白样受体B2（LILRB2）之间存在潜在联系。我们推测CSF3/CSF3R可能调节LILRB2及其配体血管生成素样蛋白2（ANGPTL2）和人类白细胞抗原G（HLA-G），从而导致免疫抑制。
目的
研究GC中CSF3/CSF3R与LILRB2及其配体ANGPTL2和HLA-G之间的关系。
方法
分析来自癌症基因组图谱的转录组测序数据，根据CSF3R表达对患者进行分层。评估差异表达基因和免疫检查点。对GC组织进行免疫组织化学（IHC）检测。使用癌症基因组图谱数据和IHC结果对CSF3R、LILRB2、ANGPTL2和HLA-G进行相关性分析。用CSF3处理GC细胞，通过定量逆转录聚合酶链反应和蛋白质免疫印迹法检测LILRB2、ANGPTL2和HLA-G的表达水平。
结果
在CSF3R高表达组的122个上调基因中，LILRB2的增加最为显著。IHC结果显示，GC组织中LILRB2（63.0%）、ANGPTL2（56.5%）和HLA-G（73.9%）高表达。CSF3R与LILRB2、ANGPTL2和HLA-G mRNA水平之间存在强正相关（<0.001）。IHC证实CSF3R与LILRB2（<0.001）和HLA-G（=0.010）之间存在正相关，但与ANGPTL2不存在正相关（>0.05）。CSF3增加了GC细胞中LILRB2、ANGPTL2和HLA-G的表达。不均一核核糖核蛋白H1调节显著改变了它们的表达，影响了CSF3的调节作用。
结论
CSF3/CSF3R通路可能通过上调LILRB2及其配体导致GC中的免疫抑制，不均一核核糖核蛋白H1起调节作用。
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