Comprehensive pan-cancer analysis reveals clinical and immunological significance of ATP7A as a potential biomarker in hepatic carcinoma

Copper death has emerged as a potent tool in clearing cancer cells. The ATPase Copper Transporting Alpha (ATP7A) plays a pivotal role in in maintaining intracellular copper ion homeostasis, yet a comprehensive pan-cancer analysis of its molecular function and clinical relevance remains elusive. In this study, we systematically examined the expression levels of ATP7A across various malignancies using data from the TCGA database, delving into its expression patterns, prognostic significance, potential regulatory impact on the immune microenvironment, as well as its association with tumor mutation burden and microsatellite instability in a pan-cancer context. Our investigation revealed downregulation of ATP7A in colon cancer, ovarian cancer, and pancreatic carcinoma, while observing upregulation in liver hepatocellular carcinoma, lung adenocarcinoma, and glioblastoma. Furthermore, heightened expression of ATP7A was found to be linked to poorer prognosis in Kidney renal clear cell carcinoma and Brain Lower Grade Glioma. Notably, ATP7A demonstrated a positive correlation with immune scores in LGG, and conversely, exhibited a negative correlation with immune scores in bladder urothelial carcinoma, breast invasive carcinoma, lung squamous cell carcinoma, and thyroid carcinoma. Leveraging Cibersortx software for the calculation of immune cell infiltration scores using global gene expression profiles of patients, we observed a strong association between ATP7A expression levels and the abundance of tumor-infiltrating immune cells. Additionally, our analysis unveiled significant correlations between ATP7A expression and PDL1 expression, tumor mutation burden (TMB), and microsatellite instability (MSI), suggesting its potential as a biomarker for immune checkpoint blockade (ICB) therapy. In summary, our study presents an encompassing pan-cancer analysis of ATP7A, providing a foundational framework for ATP7A-based precision medicine strategies.