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

BackgroundColony 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...

Full description

Bibliographic Details
Main Authors: Xingchao Wang, Jianfeng Zhang, Baoying Hu, Fei Qian
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.850767/full
_version_ 1811311434917740544
author Xingchao Wang
Jianfeng Zhang
Baoying Hu
Fei Qian
author_facet Xingchao Wang
Jianfeng Zhang
Baoying Hu
Fei Qian
author_sort Xingchao Wang
collection DOAJ
description BackgroundColony 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.MethodsCSF-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-1Rhigh and CSF-1Rlow 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.ResultsIHC 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.ConclusionCSF-1R can serve as an independent prognostic factor of COAD and promising immunotherapeutic target of COAD.
first_indexed 2024-04-13T10:18:58Z
format Article
id doaj.art-c87ecde3262e4c73a358c20da25e10da
institution Directory Open Access Journal
issn 2234-943X
language English
last_indexed 2024-04-13T10:18:58Z
publishDate 2022-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj.art-c87ecde3262e4c73a358c20da25e10da2022-12-22T02:50:37ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.850767850767High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon AdenocarcinomaXingchao Wang0Jianfeng Zhang1Baoying Hu2Fei Qian3Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Immunology, Medical College, Nantong University, Nantong, ChinaDepartment of General Surgery, Affiliated Hospital of Nantong University, Nantong, ChinaBackgroundColony 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.MethodsCSF-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-1Rhigh and CSF-1Rlow 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.ResultsIHC 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.ConclusionCSF-1R can serve as an independent prognostic factor of COAD and promising immunotherapeutic target of COAD.https://www.frontiersin.org/articles/10.3389/fonc.2022.850767/fullCSF-1Rcolon adenocarcinomaprognosispathwaytumor immunity
spellingShingle Xingchao Wang
Jianfeng Zhang
Baoying Hu
Fei Qian
High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma
Frontiers in Oncology
CSF-1R
colon adenocarcinoma
prognosis
pathway
tumor immunity
title High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma
title_full High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma
title_fullStr High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma
title_full_unstemmed High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma
title_short High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma
title_sort high expression of csf 1r predicts poor prognosis and csf 1rhigh tumor associated macrophages inhibit anti tumor immunity in colon adenocarcinoma
topic CSF-1R
colon adenocarcinoma
prognosis
pathway
tumor immunity
url https://www.frontiersin.org/articles/10.3389/fonc.2022.850767/full
work_keys_str_mv AT xingchaowang highexpressionofcsf1rpredictspoorprognosisandcsf1rhightumorassociatedmacrophagesinhibitantitumorimmunityincolonadenocarcinoma
AT jianfengzhang highexpressionofcsf1rpredictspoorprognosisandcsf1rhightumorassociatedmacrophagesinhibitantitumorimmunityincolonadenocarcinoma
AT baoyinghu highexpressionofcsf1rpredictspoorprognosisandcsf1rhightumorassociatedmacrophagesinhibitantitumorimmunityincolonadenocarcinoma
AT feiqian highexpressionofcsf1rpredictspoorprognosisandcsf1rhightumorassociatedmacrophagesinhibitantitumorimmunityincolonadenocarcinoma