Abstract
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.
Highlights
In women, breast cancer (BC) is one of the leading causes of death, and is the leading cause of cancerrelated death [1]
We used Gene Expression Profiling Interactive Analysis (GEPIA) to compare ATPase H+ transporting accessory protein 1 (ATP6AP1) mRNA levels between BC and normal tissues based on RNA sequencing data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database (Figure 1B)
We found that ATP6AP1 levels were significantly greater in BC tissues than in normal breast tissues, and correlated significantly with the cancer stage and lymph node metastasis status (N1 vs. N0)
Summary
Breast cancer (BC) is one of the leading causes of death, and is the leading cause of cancerrelated death [1]. Early detection and advanced treatment methods for BC are rapidly being developed, further research is needed to clarify the underlying pathways and prognostic factors of BC. The tumor microenvironment contributes significantly to tumor development, and is characterized by an acidic pH. Due to its function as a proton pump, V-ATPase can help cancer cells excrete excess H+, reverse the transmembrane proton gradient and form a highly acidic extracellular environment while avoiding apoptosis [5]. A recent study indicated that salivary autoantibodies against ATP6AP1 could be used as biomarkers for the early detection of BC [3]. ATP6AP1 may alter the immune microenvironment of BC and the prognoses of BC patients
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