COVID-19 Research Paper Volume 13, Issue 13 pp 16904—16921

Prognostic and immunological value of ATP6AP1 in breast cancer: implications for SARS-CoV-2

Jintian Wang1, , Yunjiang Liu1, , Shuo Zhang1, ,

  • 1 Department of Breast Surgery, The Fourth Hospital of Hebei Medical University, Hebei, Shijiazhuang 050011, China

Received: November 28, 2020       Accepted: May 11, 2021       Published: July 6, 2021
How to Cite

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Abnormal ATPase H+ Transporting Accessory Protein 1 (ATP6AP1) expression may promote carcinogenesis. We investigated the association of ATP6AP1 with breast cancer (BC) and COVID-19. The Oncomine, Gene Expression Profiling Interactive Analysis, Human Protein Atlas and Kaplan-Meier plotter databases were used to evaluate the expression and prognostic value of ATP6AP1 in BC. ATP6AP1 was upregulated in BC tissues, and higher ATP6AP1 expression was associated with poorer outcomes. Data from the Tumor Immune Estimation Resource, Tumor-Immune System Interaction Database and Kaplan-Meier plotter indicated that ATP6AP1 expression correlated with immune infiltration, and that its prognostic effects in BC depended on tumor-infiltrating immune cell subtype levels. Multiple databases were used to evaluate the association of ATP6AP1 with clinicopathological factors, assess the mutation and methylation of ATP6AP1, and analyze gene co-expression and enrichment. The ATP6AP1 promoter was hypomethylated in BC tissues and differentially methylated between different disease stages and subtypes. Data from the Gene Expression Omnibus indicated that ATP6AP1 levels in certain cell types were reduced after SARS-CoV-2 infections. Ultimately, higher ATP6AP1 expression was associated with a poorer prognosis and with higher or lower infiltration of particular immune cells in BC. BC patients may be particularly susceptible to SARS-CoV-2 infections, which may alter their prognoses.


ATP6AP1: ATPase H+ transporting accessory protein 1; BC: breast cancer; CPM: counts per million; DFS: disease-free survival; EGFR: epidermal growth factor receptor; GCBI: Gene-Cloud of Biotechnology Information; GEO: Gene Expression Omnibus; GEPIA: Gene Expression Profiling Interactive Analysis; GO: Gene Ontology; GTEx: Genotype-Tissue Expression; HPA: Human Protein Atlas; hPSC-LOs: human pluripotent stem cell-lung organoids; HSF: heat shock factor; iAT2: induced alveolar type II epithelial-like cells; KEGG: Kyoto Encyclopedia of Genes and Genomes; OS: overall survival; RFS: relapse-free survival; RPKM: reads per kilobase million; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; STRING: Search Tool for the Retrieval of Interacting Genes; TCGA: The Cancer Genome Atlas; TF: Transcription Factor; Th1 cells: type 1 T helper cells; Th2 cells: type 2 T helper cells; TIICs: tumor-infiltrating immune cells; TIMER: Tumor IMmune Estimation Resource; TISIDB: Tumor-Immune System Interaction Database; TPM: transcripts per million; Tregs: regulatory T cells; V-ATPase: Vacuole ATPase.