The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment

Background Cluster of differentiation 47 (CD47), a transmembrane protein, plays a critical role in regulating cellular functions and maintaining immune homeostasis. Its expression has been shown to influence cancer prognosis. In this study, we investigated the role of CD47 in tumor progression in co...

Full description

Saved in:
Bibliographic Details
Main Authors: Qiu-Si Tian, ChunMei Zhang, Zhi-Jun Bao, ZhiGang Pei
Format: Article
Language:English
Published: PeerJ Inc. 2024-12-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/18579.pdf
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846127608987648000
author Qiu-Si Tian
ChunMei Zhang
Zhi-Jun Bao
ZhiGang Pei
author_facet Qiu-Si Tian
ChunMei Zhang
Zhi-Jun Bao
ZhiGang Pei
author_sort Qiu-Si Tian
collection DOAJ
description Background Cluster of differentiation 47 (CD47), a transmembrane protein, plays a critical role in regulating cellular functions and maintaining immune homeostasis. Its expression has been shown to influence cancer prognosis. In this study, we investigated the role of CD47 in tumor progression in colon adenocarcinoma (COAD) and evaluated its potential as a target for immunotherapy. Materials and Methods We analyzed surgical samples from 96 COAD patients. Immunohistochemical analysis was performed on 90 samples, while the remaining 6 were subjected to multiplex immunofluorescence. To explore the association between CD47 expression and clinicopathological characteristics, we integrated transcriptome data from The Cancer Genome Atlas and the Gene Expression Omnibus using R software. The Tumor Immune Estimation Resource and Kaplan-Meier plotter were utilized to assess the relationship between CD47 expression, patient prognosis, and immune infiltration. Furthermore, the single-cell Tumor Immune System Interaction Database was used to examine the correlation between CD47 expression and the tumor microenvironment (TME). All included patients gave oral and written informed consent. The study was approved by the Ethics Committee of 3201 Hospital (full name: Medical Ethics Committee of 3201 Hospital). Results CD47 was found to be overexpressed in various tumors, including COAD. Higher CD47 expression was significantly associated with more advanced tumor stages, including TNM staging, T staging, and N staging (P < 0.05). A robust correlation was observed between CD47 expression and immune cell infiltration in COAD. Patients with elevated CD47 expression tended to have longer disease-free intervals, although this benefit was diminished in cases with high infiltration of M1 macrophages. The immunosuppressive function of CD47 primarily acted through the CD47/SIRPα pathway. Additionally, distinct cellular compositions and distributions were identified between primary and metastatic COAD, underscoring the heterogeneity of the TME. CD47 also influenced the TME by modulating cytokine and cytokine receptor interactions. Conclusion CD47 represents a promising prognostic biomarker and a potential target for immunotherapy in COAD. These findings provide new insights into therapeutic strategies aimed at modulating the TME and improving patient outcomes.
format Article
id doaj-art-6ef42bbbf0924896aa81e8a351f78b89
institution Kabale University
issn 2167-8359
language English
publishDate 2024-12-01
publisher PeerJ Inc.
record_format Article
series PeerJ
spelling doaj-art-6ef42bbbf0924896aa81e8a351f78b892024-12-11T15:05:11ZengPeerJ Inc.PeerJ2167-83592024-12-0112e1857910.7717/peerj.18579The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironmentQiu-Si Tian0ChunMei Zhang1Zhi-Jun Bao2ZhiGang Pei3Department of Neurosurgery, 3201 Hospital of Xi’an Jiaotong University Health Science Center, HanZhong, ShaanXi, ChinaDepartment of Pathology, Chongqing University Jiangjin Hospital, ChongQing, ChinaDepartment of Neurosurgery, 3201 Hospital of Xi’an Jiaotong University Health Science Center, HanZhong, ShaanXi, ChinaDepartment of Pathology, Chongqing University Jiangjin Hospital, ChongQing, ChinaBackground Cluster of differentiation 47 (CD47), a transmembrane protein, plays a critical role in regulating cellular functions and maintaining immune homeostasis. Its expression has been shown to influence cancer prognosis. In this study, we investigated the role of CD47 in tumor progression in colon adenocarcinoma (COAD) and evaluated its potential as a target for immunotherapy. Materials and Methods We analyzed surgical samples from 96 COAD patients. Immunohistochemical analysis was performed on 90 samples, while the remaining 6 were subjected to multiplex immunofluorescence. To explore the association between CD47 expression and clinicopathological characteristics, we integrated transcriptome data from The Cancer Genome Atlas and the Gene Expression Omnibus using R software. The Tumor Immune Estimation Resource and Kaplan-Meier plotter were utilized to assess the relationship between CD47 expression, patient prognosis, and immune infiltration. Furthermore, the single-cell Tumor Immune System Interaction Database was used to examine the correlation between CD47 expression and the tumor microenvironment (TME). All included patients gave oral and written informed consent. The study was approved by the Ethics Committee of 3201 Hospital (full name: Medical Ethics Committee of 3201 Hospital). Results CD47 was found to be overexpressed in various tumors, including COAD. Higher CD47 expression was significantly associated with more advanced tumor stages, including TNM staging, T staging, and N staging (P < 0.05). A robust correlation was observed between CD47 expression and immune cell infiltration in COAD. Patients with elevated CD47 expression tended to have longer disease-free intervals, although this benefit was diminished in cases with high infiltration of M1 macrophages. The immunosuppressive function of CD47 primarily acted through the CD47/SIRPα pathway. Additionally, distinct cellular compositions and distributions were identified between primary and metastatic COAD, underscoring the heterogeneity of the TME. CD47 also influenced the TME by modulating cytokine and cytokine receptor interactions. Conclusion CD47 represents a promising prognostic biomarker and a potential target for immunotherapy in COAD. These findings provide new insights into therapeutic strategies aimed at modulating the TME and improving patient outcomes.https://peerj.com/articles/18579.pdfCD47Immune escapeTumor microenvironmentCOADHeterogeneity
spellingShingle Qiu-Si Tian
ChunMei Zhang
Zhi-Jun Bao
ZhiGang Pei
The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment
PeerJ
CD47
Immune escape
Tumor microenvironment
COAD
Heterogeneity
title The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment
title_full The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment
title_fullStr The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment
title_full_unstemmed The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment
title_short The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment
title_sort role of cd47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment
topic CD47
Immune escape
Tumor microenvironment
COAD
Heterogeneity
url https://peerj.com/articles/18579.pdf
work_keys_str_mv AT qiusitian theroleofcd47inimmuneescapeofcoloncanceranditscorrelationwithheterogeneityoftumorimmunemicroenvironment
AT chunmeizhang theroleofcd47inimmuneescapeofcoloncanceranditscorrelationwithheterogeneityoftumorimmunemicroenvironment
AT zhijunbao theroleofcd47inimmuneescapeofcoloncanceranditscorrelationwithheterogeneityoftumorimmunemicroenvironment
AT zhigangpei theroleofcd47inimmuneescapeofcoloncanceranditscorrelationwithheterogeneityoftumorimmunemicroenvironment
AT qiusitian roleofcd47inimmuneescapeofcoloncanceranditscorrelationwithheterogeneityoftumorimmunemicroenvironment
AT chunmeizhang roleofcd47inimmuneescapeofcoloncanceranditscorrelationwithheterogeneityoftumorimmunemicroenvironment
AT zhijunbao roleofcd47inimmuneescapeofcoloncanceranditscorrelationwithheterogeneityoftumorimmunemicroenvironment
AT zhigangpei roleofcd47inimmuneescapeofcoloncanceranditscorrelationwithheterogeneityoftumorimmunemicroenvironment