Exploration of the immune microenvironment of breast cancer in large population cohorts

Tumor immune microenvironment is associated with tumor progression. However, previous studies have not fully explored the breast cancer (BC) immune microenvironment. All the data analyzed in this study were obtained from the open-access database, including The Cancer Genome Atlas, Gene Expression Om...

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Main Authors: Youyuan Deng, Jianguo Wang, Zhiya Hu, Yurong Cai, Yiping Xu, Ke Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2022.955630/full
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author Youyuan Deng
Jianguo Wang
Zhiya Hu
Yurong Cai
Yiping Xu
Ke Xu
Ke Xu
Ke Xu
author_facet Youyuan Deng
Jianguo Wang
Zhiya Hu
Yurong Cai
Yiping Xu
Ke Xu
Ke Xu
Ke Xu
author_sort Youyuan Deng
collection DOAJ
description Tumor immune microenvironment is associated with tumor progression. However, previous studies have not fully explored the breast cancer (BC) immune microenvironment. All the data analyzed in this study were obtained from the open-access database, including The Cancer Genome Atlas, Gene Expression Omnibus (TCGA), and cBioPortal databases. R software v4.0 and SPSS 13.0 were used to perform all the statistical analysis. Firstly, the clinical and expression profile information of TCGA, GSE20685, GSE20711, GSE48390, GSE58812, and METABRIC cohorts was collected. Then, 53 immune terms were quantified using the single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. A prognosis model based on HER2_Immune_PCA, IL12_score, IL13_score, IL4_score, and IR7_score was established, which showed great prognosis prediction efficiency in both training group and validation group. A nomogram was then established for a better clinical application. Clinical correlation showed that elderly BC patients might have a higher riskscore. Pathway enrichment analysis showed that the pathway of oxidative phosphorylation, E2F targets, hedgehog signaling, adipogenesis, DNA repair, glycolysis, heme metabolism, and mTORC1 signaling was activated in the high-risk group. Moreover, Tumor Immune Dysfunction and Exclusion and Genomics of Drug Sensitivity in Cancer analysis showed that low-risk patients might be more sensitive to PD-1 therapy, cisplatin, gemcitabine, paclitaxel, and sunitinib. Finally, four genes, XCL1, XCL2, TNFRSF17, and IRF4, were identified for risk group classification. In summary, our signature is a useful tool for the prognosis and prediction of the drug sensitivity of BC.
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spelling doaj.art-4fe62efa1490448aacf4c05a29bbbf292022-12-22T03:44:04ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-08-011310.3389/fendo.2022.955630955630Exploration of the immune microenvironment of breast cancer in large population cohortsYouyuan Deng0Jianguo Wang1Zhiya Hu2Yurong Cai3Yiping Xu4Ke Xu5Ke Xu6Ke Xu7Department of General Surgery, Xiangtan Central Hospital, Xiangtan, ChinaDepartment of General Surgery, Xiangtan Central Hospital, Xiangtan, ChinaDepartment of Pharmacy, Third Hospital of Changsha, Changsha, ChinaDepartment of General Surgery, Xiangtan Central Hospital, Xiangtan, ChinaDepartment of General Surgery, Xiangtan Central Hospital, Xiangtan, ChinaDepartment of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, ChinaClinical Medical College, Chengdu Medical College, Chengdu, ChinaKey Clinical Specialty of Sichuan Province, Chengdu, ChinaTumor immune microenvironment is associated with tumor progression. However, previous studies have not fully explored the breast cancer (BC) immune microenvironment. All the data analyzed in this study were obtained from the open-access database, including The Cancer Genome Atlas, Gene Expression Omnibus (TCGA), and cBioPortal databases. R software v4.0 and SPSS 13.0 were used to perform all the statistical analysis. Firstly, the clinical and expression profile information of TCGA, GSE20685, GSE20711, GSE48390, GSE58812, and METABRIC cohorts was collected. Then, 53 immune terms were quantified using the single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. A prognosis model based on HER2_Immune_PCA, IL12_score, IL13_score, IL4_score, and IR7_score was established, which showed great prognosis prediction efficiency in both training group and validation group. A nomogram was then established for a better clinical application. Clinical correlation showed that elderly BC patients might have a higher riskscore. Pathway enrichment analysis showed that the pathway of oxidative phosphorylation, E2F targets, hedgehog signaling, adipogenesis, DNA repair, glycolysis, heme metabolism, and mTORC1 signaling was activated in the high-risk group. Moreover, Tumor Immune Dysfunction and Exclusion and Genomics of Drug Sensitivity in Cancer analysis showed that low-risk patients might be more sensitive to PD-1 therapy, cisplatin, gemcitabine, paclitaxel, and sunitinib. Finally, four genes, XCL1, XCL2, TNFRSF17, and IRF4, were identified for risk group classification. In summary, our signature is a useful tool for the prognosis and prediction of the drug sensitivity of BC.https://www.frontiersin.org/articles/10.3389/fendo.2022.955630/fullbreast cancerimmunedrugprognosissignature
spellingShingle Youyuan Deng
Jianguo Wang
Zhiya Hu
Yurong Cai
Yiping Xu
Ke Xu
Ke Xu
Ke Xu
Exploration of the immune microenvironment of breast cancer in large population cohorts
Frontiers in Endocrinology
breast cancer
immune
drug
prognosis
signature
title Exploration of the immune microenvironment of breast cancer in large population cohorts
title_full Exploration of the immune microenvironment of breast cancer in large population cohorts
title_fullStr Exploration of the immune microenvironment of breast cancer in large population cohorts
title_full_unstemmed Exploration of the immune microenvironment of breast cancer in large population cohorts
title_short Exploration of the immune microenvironment of breast cancer in large population cohorts
title_sort exploration of the immune microenvironment of breast cancer in large population cohorts
topic breast cancer
immune
drug
prognosis
signature
url https://www.frontiersin.org/articles/10.3389/fendo.2022.955630/full
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