Integrative landscape analysis of prognostic model biomarkers and immunogenomics of disulfidptosis-related genes in breast cancer based on LASSO and WGCNA analyses

Abstract

BackgroundDisulfidptosis is a novel type of programmed cell death. However, the value of disulfidptosis-related genes (DRGs) in the prediction of breast cancer prognosis is unclear.MethodsRNA-seq data of 1231 patients, together with information on patient clinical characteristics and prognosis, were downloaded from TCGA. DRGs were identified between cancerous and non-cancerous tissues. The LASSO algorithm was used to assign half of the samples to the training set. Risk scores were used for construction of a prognostic model for risk stratification and prognosis prediction, and the clinical applicability was examined using a line diagram. The relationships between risk scores, immune cell infiltration, molecular subtypes, and responses to immunotherapy and chemotherapy were examined.ResultsWe identified and obtained four DRG-related prognostic lncRNAs (AC009097.2, AC133552.5, YTHDF3-AS1, and AC084824.5), which were used for establishing the risk model. Longer survival was associated with low risk. The DRG-associated lncRNAs were found to independently predict patient prognosis. The AUCs under the ROCs for one-, three-, and 5-year survival in the training cohort were 0.720, 0.687, and 0.692, respectively. The model showed that the high-risk patients had reduced overall survival as well as high tumor mutation burdens. Furthermore, high-risk patients showed increased sensitivity to therapeutic drugs, including docetaxel, paclitaxel, and oxaliplatin.ConclusionThe risk score model was effective for predicting both prognosis and sensitivity to therapeutic drugs, suggesting its possible usefulness for the management of patients with breast cancer.