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CSF-1R的高表达预示结肠癌预后不良，且CSF-1R肿瘤相关巨噬细胞抑制抗肿瘤免疫。

High Expression of CSF-1R Predicts Poor Prognosis and CSF-1R Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma.

作者信息

Wang Xingchao, Zhang Jianfeng, Hu Baoying, Qian Fei

机构信息

Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China.

Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

Front Oncol. 2022 Apr 4;12:850767. doi: 10.3389/fonc.2022.850767. eCollection 2022.

DOI:10.3389/fonc.2022.850767
PMID:35444953
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9014714/
Abstract

BACKGROUND

Colony stimulating factor 1 receptor (CSF-1R) is a single channel III transmembrane receptor tyrosine kinase (RTK) and plays an important role in immune regulation and the development of various cancer types. The expression of CSF-1R in colon adenocarcinoma (COAD) and its prognostic value remain incompletely understood. Therefore, we aim to explore the prognostic value of CSF-1R in COAD and its relationship with tumor immunity.

METHODS

CSF-1R expression in a COAD cohort containing 103 patients was examined using immunohistochemistry (IHC). The relationship between CSF-1R expression and clinicopathological parameters and prognosis was evaluated. Dual immunofluorescence staining was conducted to determine the localization of CSF-1R in COAD tissues. Univariate and multivariate Cox regression analysis were performed to evaluate independent prognostic factors. Transcriptomic profiles of CSF-1R and CSF-1R tumor-associated macrophages (TAMs) were investigated. Gene enrichment analysis was used to explore the signal pathways related to CSF-1R. In addition, the relationship between CSF-1R in tumor microenvironment (TME) and tumor immunity was also studied.

RESULTS

IHC analysis showed that CSF-1R was overexpressed in COAD, and higher expression was associated with shorter overall survival (OS). Immunofluorescence staining showed that CSF-1R was co-localized with macrophage marker CD68. Univariate and multivariate Cox regression analysis showed that CSF-1R was an independent prognostic factor for COAD. The results of gene enrichment analysis showed that CSF-1R was involved in tumor immune response and regulation of TME. In addition, CSF-1R was significantly correlated with TME, immune cell infiltration, TMB, MSI, Neoantigen, and immune checkpoint molecules.

CONCLUSION

CSF-1R can serve as an independent prognostic factor of COAD and promising immunotherapeutic target of COAD.

摘要

背景

集落刺激因子1受体（CSF-1R）是一种单通道III型跨膜受体酪氨酸激酶（RTK），在免疫调节和多种癌症类型的发展中起重要作用。CSF-1R在结肠腺癌（COAD）中的表达及其预后价值仍未完全明确。因此，我们旨在探讨CSF-1R在COAD中的预后价值及其与肿瘤免疫的关系。

方法

使用免疫组织化学（IHC）检测了一个包含103例患者的COAD队列中CSF-1R的表达。评估了CSF-1R表达与临床病理参数及预后的关系。进行双重免疫荧光染色以确定CSF-1R在COAD组织中的定位。进行单因素和多因素Cox回归分析以评估独立预后因素。研究了CSF-1R和CSF-1R肿瘤相关巨噬细胞（TAM）的转录组谱。基因富集分析用于探索与CSF-1R相关的信号通路。此外，还研究了肿瘤微环境（TME）中CSF-1R与肿瘤免疫的关系。

结果

IHC分析显示CSF-1R在COAD中过表达，且较高表达与较短的总生存期（OS）相关。免疫荧光染色显示CSF-1R与巨噬细胞标志物CD68共定位。单因素和多因素Cox回归分析表明CSF-1R是COAD的独立预后因素。基因富集分析结果显示CSF-1R参与肿瘤免疫反应和TME调节。此外，CSF-1R与TME、免疫细胞浸润、肿瘤突变负荷（TMB）、微卫星高度不稳定（MSI）、新抗原和免疫检查点分子显著相关。

结论

CSF-1R可作为COAD的独立预后因素及有前景的免疫治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/079e/9014714/9300bb733b61/fonc-12-850767-g007.jpg
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