Transcriptome network analysis identifies co-expressed CXCL13, CXCR5, and associated genes contributes to the aggressive phenotype of TNBC

Abstract

Abstract Triple negative breast cancer (TNBC) is an aggressive disease associated with poor prognosis. Currently, there are no targeted therapies for this disease. Standard therapy for TNBC consists of a combination of chemotherapeutic drugs. However, patients often become resistant to this intervention and ultimately succumb to this disease. Hence, understanding the cellular and molecular mechanisms associated with TNBC progression is essential to develop more effective therapies. We hypothesize co-expressed CXCL13, CXCR5, and associated genes are significantly correlated with TNBC and poor overall survival. A bioinformatic approach was used to characterize this new potential drug target for TNBC. Our patient cohort was obtained from The Cancer Genome Atlas. Weighted gene network co-expression analysis identified gene networks associated with factors influencing BrCa prognosis. An ANOVA test identified genes differentially expressed among Luminal A, Luminal B, HER-2, and TNBC tumor groups. Finally, gene ontology analysis was performed via GO-ELITE and EPIC was used to estimate the proportion of various cell types found in bulk samples. We identified seven unique gene networks that were significantly and positively correlated with TNBC. The turquoise module (M1), contained CXCL13, CXCR5, and associated genes that drive tertiary lymphoid structure formation, regulation of immune response, and immune system processes. The M1 module was also significantly and positively correlated with TNBC, but not overall survival. The genes signatures contained in the M1 module were significantly correlated to CD8+ T cell, macrophage, B cell, CD4+ T cell, cancer-associated fibroblast, and NK cell, as determined by EPIC analysis.