Identification of a prognostic chemoresistance-related gene signature associated with immune microenvironment in breast cancer.

ABSTRACT

Breast cancer is the most common form of cancer among women globally, and chemoresistance is a major challenge to disease treatment that is associated with a poor prognosis. This study was formulated to identify a reliable prognostic biosignature capable of predicting the survival of patients with chemoresistant breast cancer (CRBC) and evaluating the associated tumor immune microenvironment. Through a series of protein-protein interaction and weighted correlation network analyses, genes that were significantly associated with breast cancer chemoresistance were identified. Moreover, univariate Cox regression and lasso-penalized Cox regression analyses were employed to generate a prognostic model, and the prognostic utility of this model was then assessed using time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curves. Finally, The CIBERSORT and ESTIMATE algorithms were additionally leveraged to assess relationships between the tumor immune microenvironment and patient prognostic signatures. Overall, a multigenic prognostic biosignature capable of predicting CRBC patient risk was successfully developed based on bioinformatics analysis and in vitro experiments. This biosignature was able to stratify CRBC patients into high- and low-risk subgroups. ROC curves also revealed that this biosignature achieved high diagnostic efficiency, and multivariate regression analyses indicated that this risk signature was an independent risk factor linked to CRBC patient outcomes. In addition, this signature was associated with the infiltration of the tumor microenvironment by multiple immune cell types. In conclusion, the chemoresistance-associated prognostic gene signature developed herein was able to effectively evaluate the prognosis of CRBC patients and to reflect the overall composition of the tumor immune microenvironment.