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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Frontiers Media S.A.
2022-06-01
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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. |
first_indexed | 2024-12-12T07:55:16Z |
format | Article |
id | doaj.art-8b11ba17ade2491ca30993a4bda758f2 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-12-12T07:55:16Z |
publishDate | 2022-06-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Immunology |
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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