Identification of a disulfidptosis-correlated ferroptosis prognostic model in breast cancer.

Targeting the urgent need for diagnostic biomarkers in breast cancer, the most common female malignancy, this study evaluates the diagnostic and prognostic potential of disulfidptosis-related ferroptosis genes (DRFGs), leveraging the emerging roles of disulfidptosis and ferroptosis in cancer biology. Ferroptosis- and disulfidptosis-related genes of patients with breast cancer were collected from The Cancer Genome Atlas database, then 154 identified prognosis-associated DRFGs were analyzed using Pearson correlation analysis, and developed a DRFG-associated risk model containing 19 DRFGs by applying the least absolute shrinkage and selection operator Cox regression analysis. We then assessed the prognostic performance of the risk model between the high- and low-risk groups. The risk scores and clinical variables were combined to construct a nomogram. Bioinformatics analyses including functional enrichment analysis and protein-protein interaction networks were conducted. Besides, we examined the biological functions, immune checkpoints, and drug sensitivity of the model. Finally, ANO6 overexpression effects on breast cancer cell invasion and metastasis were examined via wound healing and Transwell assays. The high-risk group showed poorer overall survival (OS) rates (P <.001) and lower receiver operating characteristic curve area under receiver operating characteristic values compared to the low-risk group. The results of univariate and multivariate Cox regression analyses confirmed that the established nomogram model served as an independent prognostic indicator. Functional enrichment analysis revealed the involvement of DRFGs in biological processes and signaling pathways beyond disulfidptosis and ferroptosis. The level of expressions of immune checkpoints for TDO2 and PVR were increased in the high-risk group. Drug sensitivity analysis showed that high-risk patients benefited more from AKT.inhibitor.VIII. Moreover, anoctamin 6 overexpression inhibited breast cancer cell invasion and metastasis. This study successfully established a DRFG-related prognostic model for patients with breast cancer, and anoctamin 6 has emerged as a promising therapeutic target for breast cancer.