M2 Macrophage Co-Expression Factors Correlate With Immune Phenotype and Predict Prognosis of Bladder Cancer.

Yutao Wang,Jianfeng Wang,Jiaxing Lin,Jianbin Bi,Kexin Yan

doi:10.3389/fonc.2021.609334

Yutao Wang, Jianfeng Wang + Show 3 more

Open Access

https://doi.org/10.3389/fonc.2021.609334

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Abstract

PurposeTherapeutic targets of tumor-associated macrophages have been discovered and used clinically as immunotherapy. M2 macrophages are tumor-associated macrophages that promote cancer progression. This article explores the related factors and the effects of type M2 macrophages.MethodWe obtained bladder cancer (BC) sequencing data from TCGA and GSE31189. We used the CIBERSORT algorithm calculate M2 macrophage proportions among 22 type immune cells. The Estimate package was used to measure BC purity. M2 macrophage-related genes were selected using WGCNA. Receiver operating characteristic curves and Kaplan–Meier analyses were performed to determine the risk score, conducted for M2 macrophage-related factors. The Pearson test was used to determine the correlation among M2 macrophage-related genes, clinical phenotype, immune phenotype and tumor mutation burden (TMB). The TIMER database was used to calculate correlations among M2 macrophages and other cancers.ResultsExpression of four M2 macrophages co-expressed genes (CD163, CD209, CSF1, MMD) positively correlated with infiltration of M2 macrophages, which were enriched in the negative regulation of immune system process and the positive regulation of tumor necrosis factor production. M2 macrophage-related factors are robust biomarkers for predicting the BC and immune phenotypes. The Cox regression model built on these four co-expression factors showed a close correlation with outcome (AUC = 0.64). The four co-expression factors negatively correlated outcome and TMB.ConclusionFour co-expressed genes promote high levels of infiltration of type M2 macrophages in the negative regulation of immune system processes and the positive regulation of tumor necrosis factor production processes. These co-expressed genes and the biological process they involve might suggest new strategies for regulation of chemotaxis in M2 macrophages.

Highlights

Bladder cancer (BC) ranks fourth among the most common tumors in developed countries [1]
The results showed that the macrophage proportions were the highest in bladder tumor microenvironment
M2 macrophages acted as risk prognosis factor (Table 1)

Summary

Introduction

Bladder cancer (BC) ranks fourth among the most common tumors in developed countries [1]. Immunotherapy for advanced BC has attracted increasing attention. BC is characterized by a high mutation rate and many new tumor antigens, and it is relatively sensitive to immunotherapy [3]. Immune regulation plays a key role in BC. This process includes immune checkpoints (primarily programmed cell death 1 [PD-1 and programmed cell death 1 ligand 1 [PD-L1), as well as regulatory T cells, original source of suppressor cells and tumor-associated macrophages (TAM; macrophages in primary or secondary tumor tissues) and type 2 innate and adaptive lymphocytes [4]. Clinical and experimental evidence suggested that macrophages promote the progression and metastasis of solid tumors [5, 6]. Targeting macrophages has become a new treatment strategy [7, 8]. TAMs are divided into two types, M1 and M2 [9]

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