Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic Genes

Triple negative breast cancer (TNBC) remains the worst molecular subtype due to high heterogeneity and lack of effective therapeutic targets. Here we investigated the tumor and immune microenvironment heterogeneity of TNBC using scRNA-seq and bulk RNA-seq data from public databases and our cohort. M...

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Main Authors: Baojin Xu, Hefen Sun, Xiaoqing Song, Qiqi Liu, Wei Jin
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.923481/full
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author Baojin Xu
Baojin Xu
Baojin Xu
Hefen Sun
Hefen Sun
Xiaoqing Song
Xiaoqing Song
Qiqi Liu
Qiqi Liu
Wei Jin
Wei Jin
author_facet Baojin Xu
Baojin Xu
Baojin Xu
Hefen Sun
Hefen Sun
Xiaoqing Song
Xiaoqing Song
Qiqi Liu
Qiqi Liu
Wei Jin
Wei Jin
author_sort Baojin Xu
collection DOAJ
description Triple negative breast cancer (TNBC) remains the worst molecular subtype due to high heterogeneity and lack of effective therapeutic targets. Here we investigated the tumor and immune microenvironment heterogeneity of TNBC using scRNA-seq and bulk RNA-seq data from public databases and our cohort. Macrophage subpopulations accounted for a high proportion of tumor immune microenvironment (TIME), and M1 macrophages were associated with better clinical outcomes. Furthermore, three maker genes including IFI35, PSMB9, and SAMD9L showed a close connection with M1 macrophages. Specifically, IFI35 was positively associated with macrophage activation, chemotaxis, and migration. Also, patients with high IFI35 expression had a better prognosis. In vitro studies subsequently demonstrated that IFI35 was upregulated during the M1 subtype differentiation of macrophages. In summary, our data suggested that IFI35 maybe a promising novel target that helps to reshape macrophage polarization towards the M1 subtype for anti-tumor effects.
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spelling doaj.art-8b11ba17ade2491ca30993a4bda758f22022-12-22T00:32:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.923481923481Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic GenesBaojin Xu0Baojin Xu1Baojin Xu2Hefen Sun3Hefen Sun4Xiaoqing Song5Xiaoqing Song6Qiqi Liu7Qiqi Liu8Wei Jin9Wei Jin10Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Breast Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaTriple negative breast cancer (TNBC) remains the worst molecular subtype due to high heterogeneity and lack of effective therapeutic targets. Here we investigated the tumor and immune microenvironment heterogeneity of TNBC using scRNA-seq and bulk RNA-seq data from public databases and our cohort. Macrophage subpopulations accounted for a high proportion of tumor immune microenvironment (TIME), and M1 macrophages were associated with better clinical outcomes. Furthermore, three maker genes including IFI35, PSMB9, and SAMD9L showed a close connection with M1 macrophages. Specifically, IFI35 was positively associated with macrophage activation, chemotaxis, and migration. Also, patients with high IFI35 expression had a better prognosis. In vitro studies subsequently demonstrated that IFI35 was upregulated during the M1 subtype differentiation of macrophages. In summary, our data suggested that IFI35 maybe a promising novel target that helps to reshape macrophage polarization towards the M1 subtype for anti-tumor effects.https://www.frontiersin.org/articles/10.3389/fimmu.2022.923481/fulltriple negative breast cancertumor immune microenvironmentmacrophagesIFI35ScRNA-seq analysisbulk-RNA sequencing
spellingShingle Baojin Xu
Baojin Xu
Baojin Xu
Hefen Sun
Hefen Sun
Xiaoqing Song
Xiaoqing Song
Qiqi Liu
Qiqi Liu
Wei Jin
Wei Jin
Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic Genes
Frontiers in Immunology
triple negative breast cancer
tumor immune microenvironment
macrophages
IFI35
ScRNA-seq analysis
bulk-RNA sequencing
title Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic Genes
title_full Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic Genes
title_fullStr Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic Genes
title_full_unstemmed Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic Genes
title_short Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic Genes
title_sort mapping the tumor microenvironment in tnbc and deep exploration for m1 macrophages associated prognostic genes
topic triple negative breast cancer
tumor immune microenvironment
macrophages
IFI35
ScRNA-seq analysis
bulk-RNA sequencing
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.923481/full
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