A new prognostic signature based on cancer associated fibroblast-driven genes in breast cancer

Abstract

Background Breast cancer, a leading malignant disease, affects women all over the world. Cancer associated fibroblasts (CAFs) stimulate epithelial-mesenchymal transition, and induce chemoresistance and immunosuppression. Objective This study aims to establish a CAFs-associated prognostic signature to improve BC patient outcome estimation. Methods We retrieved the transcript profile and clinical data of 1072 BC samples from TCGA databases, and 3661 BC samples from the GEO. CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm. CAF-associated gene identification was done by WGCNA. A CAF risk signature was established via univariate, LASSO regression, and multivariate Cox regression analyses. The receiver operating characteristic (ROC) and Kaplan-Meier curves were employed to evaluate the predictability of the model. Subsequently, a nomogram was developed with the risk score and patient clinical signature. Using Spearman's correlations analysis, the relationship between CAF risk score and gene set enrichment scores were examined. Results Employing an 8-gene (IL18, MYD88, GLIPR1, TNN, BHLHE41, DNAJB5, FKBP14, and XG) signature, we attempted to estimate BC patient prognosis. Based on our analysis, high-risk patients exhibited worse outcomes than low-risk patients. Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis. ROC analysis exhibited satisfactory nomogram predictability. The AUC showed 0.805 at 3 years, and 0.801 at 5 years in the TCGA cohort. We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes. CAF risk score was significantly correlated with most hallmark gene sets. Conclusion We introduced a newly-discovered CAFs-linked gene signature, which served as an independent marker of BC patient prognosis.