AMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer

BackgroundAlthough immunotherapy has been used in the treatment of metastatic triple negative breast cancer (TNBC), its therapeutic influence on human epidermal growth factor receptor 2 (HER2)-positive subtype remains controversial. It is therefore imperative to find biomarkers that can predict the...

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Autores principales: Long Wang, Xue Zhang, Mengxue Wang, Yunhai Li, Jiali Xu, Jiaying Wei, Hongzhong Li, Guosheng Ren, Xuedong Yin
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:b1b49b8e9b304d6ebdae4cb24b502b3a2021-11-09T05:59:55ZAMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer2234-943X10.3389/fonc.2021.749135https://doaj.org/article/b1b49b8e9b304d6ebdae4cb24b502b3a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.749135/fullhttps://doaj.org/toc/2234-943XBackgroundAlthough immunotherapy has been used in the treatment of metastatic triple negative breast cancer (TNBC), its therapeutic influence on human epidermal growth factor receptor 2 (HER2)-positive subtype remains controversial. It is therefore imperative to find biomarkers that can predict the immune response in HER2+ BC.MethodsESTIMATE was utilized to compute the ImmuneScore and StromalScore from data obtained from TCGA database, and differentially expressed genes (DEGs) were identified. In addition, univariate Cox regression was used to assess candidate genes such as AMPD1, CD33, and CCR5. Gene set enrichment analysis (GSEA) was used to further understand AMPD1-associated pathways. Moreover, immunohistochemical analyses were performed to further reveal the relationship among AMPD1, CD4 and CD8 genes.ResultsThe expression of AMPD1 was markedly associated with disease outcome and tumor-infiltrating immune cells (TICs). In addition, AMPD1 was associated with lymph node status, age and the expression of PD-L1 and PD-L2. High AMPD1 expression was linked to longer overall survival (OS). Upregulated expression of AMPD1 correlated with the enrichment of immune-related signaling pathways. In addition, immunohistochemical analyses demonstrated a co-expression profile among AMPD1, CD4 and CD8 genes.ConclusionsTaken together, our data demonstrated that AMPD1 might serve as a novel biomarker for predicting the immune response and disease outcome in HER2+ BC.Long WangLong WangXue ZhangMengxue WangMengxue WangYunhai LiJiali XuJiali XuJiaying WeiHongzhong LiGuosheng RenGuosheng RenXuedong YinFrontiers Media S.A.articleHER2-positive breast cancerAMPD1tumor microenvironmenttumor-infiltrating immune cellsimmunotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic HER2-positive breast cancer
AMPD1
tumor microenvironment
tumor-infiltrating immune cells
immunotherapy
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle HER2-positive breast cancer
AMPD1
tumor microenvironment
tumor-infiltrating immune cells
immunotherapy
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Long Wang
Long Wang
Xue Zhang
Mengxue Wang
Mengxue Wang
Yunhai Li
Jiali Xu
Jiali Xu
Jiaying Wei
Hongzhong Li
Guosheng Ren
Guosheng Ren
Xuedong Yin
AMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer
description BackgroundAlthough immunotherapy has been used in the treatment of metastatic triple negative breast cancer (TNBC), its therapeutic influence on human epidermal growth factor receptor 2 (HER2)-positive subtype remains controversial. It is therefore imperative to find biomarkers that can predict the immune response in HER2+ BC.MethodsESTIMATE was utilized to compute the ImmuneScore and StromalScore from data obtained from TCGA database, and differentially expressed genes (DEGs) were identified. In addition, univariate Cox regression was used to assess candidate genes such as AMPD1, CD33, and CCR5. Gene set enrichment analysis (GSEA) was used to further understand AMPD1-associated pathways. Moreover, immunohistochemical analyses were performed to further reveal the relationship among AMPD1, CD4 and CD8 genes.ResultsThe expression of AMPD1 was markedly associated with disease outcome and tumor-infiltrating immune cells (TICs). In addition, AMPD1 was associated with lymph node status, age and the expression of PD-L1 and PD-L2. High AMPD1 expression was linked to longer overall survival (OS). Upregulated expression of AMPD1 correlated with the enrichment of immune-related signaling pathways. In addition, immunohistochemical analyses demonstrated a co-expression profile among AMPD1, CD4 and CD8 genes.ConclusionsTaken together, our data demonstrated that AMPD1 might serve as a novel biomarker for predicting the immune response and disease outcome in HER2+ BC.
format article
author Long Wang
Long Wang
Xue Zhang
Mengxue Wang
Mengxue Wang
Yunhai Li
Jiali Xu
Jiali Xu
Jiaying Wei
Hongzhong Li
Guosheng Ren
Guosheng Ren
Xuedong Yin
author_facet Long Wang
Long Wang
Xue Zhang
Mengxue Wang
Mengxue Wang
Yunhai Li
Jiali Xu
Jiali Xu
Jiaying Wei
Hongzhong Li
Guosheng Ren
Guosheng Ren
Xuedong Yin
author_sort Long Wang
title AMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer
title_short AMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer
title_full AMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer
title_fullStr AMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer
title_full_unstemmed AMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer
title_sort ampd1 is associated with the immune response and serves as a prognostic marker in her2-positive breast cancer
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/b1b49b8e9b304d6ebdae4cb24b502b3a
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