Abstract
PURPOSE: Zinc homeostasis and zinc transporter (ZHT) have been closely associated with the development of various cancers. Therefore, in this study, prognostic genes and their mechanisms related to ZHT in breast cancer (BC) were explored. PATIENTS AND METHODS: Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were utilized to identify genes associated with Zinc homeostasis and Zinc transporter-related genes (ZHTGs) in BC. Subsequently, independent prognostic factors and their correlations with clinical features were examined to investigate their association with the prognosis of BC. Finally, we further explored the pathways and immune cells associated with BC prognosis. We also verified gene expression in tissues and cells by quantitative polymerase chain reaction (qPCR). RESULTS: In this study, six prognostic genes were identified. Patients were subsequently classified into high-risk and low-risk cohorts based on the median risk score, with the low-risk group presenting superior survival outcomes. Subsequently, riskScore, age, tumor/node/metastasis (T/N/M) stage showed significant associations with the prognosis of BC, and the constructed nomogram demonstrated strong predictive performance. Clinical analysis revealed differences in risk scores among sub-cohorts with different clinical characteristics, such as race (white and others) and T-stage (T1 and T2, T1 and T3). Furthermore, significant disparities were noted in immune cells and immune checkpoints across different risk cohorts. The results of reverse transcription quantitative PCR were basically consistent with the prediction. In addition, the IHC results from the Human Protein Atlas database further validated our prediction. CONCLUSION: We screened six prognosis genes related to ZHT in BC, providing a reference for the prognosis and personalized treatment of BC.