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

Long Wang; Xue Zhang; Mengxue Wang; Yunhai Li; Jiali Xu; Jiaying Wei; Hongzhong Li; Guosheng Ren; Xuedong Yin

doi:10.3389/fonc.2021.749135

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

Front Oncol. 2021 Nov 9:11:749135. doi: 10.3389/fonc.2021.749135. eCollection 2021.

Authors

Long Wang^{1

2}, Xue Zhang¹, Mengxue Wang^{1

2}, Yunhai Li¹, Jiali Xu^{1

2}, Jiaying Wei¹, Hongzhong Li², Guosheng Ren^{1

2}, Xuedong Yin¹

Affiliations

¹ Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract

Background: Although 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.

Methods: ESTIMATE 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.

Results: The 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.

Conclusions: Taken together, our data demonstrated that AMPD1 might serve as a novel biomarker for predicting the immune response and disease outcome in HER2+ BC.

Keywords: AMPD1; HER2-positive breast cancer; immunotherapy; tumor microenvironment; tumor-infiltrating immune cells.