AUTHOR=Tian Ye , Gao Ming , Huang Liang , Zhou Hu , Wang Juan TITLE=ATP6AP1 is a potential prognostic biomarker and is associated with iron metabolism in breast cancer JOURNAL=Frontiers in Genetics VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.958290 DOI=10.3389/fgene.2022.958290 ISSN=1664-8021 ABSTRACT=

Cancer occurrence and progression may be facilitated by aberrant expression of ATPase H+ transporting accessory protein 1 (ATP6AP1). However, the clinical relevance of ATP6AP1 in breast cancer remains unclear. In this study, we investigated the association between ATP6AP1 and breast cancer. Data collected from patients with breast cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used in this study. To determine the relationship between ATP6AP1 and breast cancer survival rates, Kaplan-Meier analysis was used. To determine the prognostic value of ATP6AP1, a receiver operating characteristic (ROC) curve was constructed. To identify the major pathways involving ATP6AP1, we performed functional enrichment analysis using gene set enrichment analysis (GSEA). We analyzed the association between ATP6AP1 expression and tumor immunity using the ESTIMATE algorithm and single-sample GSEA (ssGSEA). A nomogram based on a Cox regression analysis was constructed to predict the impact of ATP6AP1 on prognosis. ATP6AP1 expression was significantly upregulated in breast cancer tissues. Moreover, patients with elevated ATP6AP1 expression had shorter total survival rates than those with lower expression levels (p = 0.032). The area under the receiver operating characteristic curve for ATP6AP1 was 0.939. Gene set enrichment analysis revealed that reaction iron uptake and transport, proteasome degradation, glutathione metabolism, and pyruvate metabolism were enriched in the ATP6AP1 high expression phenotype. The relationship between immune infiltration cells and ATP6AP1 expression, including macrophages, B cells, dendritic cells, cytotoxic cells, NK cells, and T cells, was found to be negative, suggesting that ATP6AP1 overexpression results in immunosuppression. Based on the Cox regression analyses, the calibration plot of the nomogram demonstrated effective performance in predicting breast cancer patients. ATP6AP1 may facilitate breast cancer progression by inhibiting antitumor immunity and promoting iron metabolism and may be a biomarker for breast cancer prognosis.