Deciphering the prognostic landscape of triple-negative breast cancer: A focus on immune-related hub genes and therapeutic implications.

Abstract

Triple-negative breast cancer (TNBC), known for its hostile nature and limited treatment modalities, has spurred researchers to explore novel approaches for enhancing clinical outcomes. Here, the study aimed to analyze transcriptomics data to identify immune-related hub genes associated with TNBC that might serve as prognostic biomarkers. Initially, we determined genes that were differentially expressed between TNBC and normal tissues by integrating microarray and RNA sequencing data. Then, through protein-protein interaction and module analysis, we identified five putative hub genes: AURKA, CCNB1, CDCA8, GAPDH, and TOP2A. Subsequently, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the hub genes were primarily involved in the progesterone-mediated oocyte maturation signaling pathway and oocyte meiosis. Additionally, we observed that these five hub genes were significantly elevated at both protein and mRNA levels in TNBC tissues and contributed to worse survival. Furthermore, the expression of these hub genes exhibited a strong positive association with immune-invading cells such as CD8 T cells, CD4 T cells, and dendritic cells. The analysis of the regulatory network revealed three transcription factors (YBX-1, E2F1, and E2F3) and three posttranscriptional regulators (hsa-mir-25-3p, hsa-mir-92a-3p, and hsa-let-7b-5p) of hub genes. Finally, we explored potential drug candidates for the hub genes using Drug-Gene Interaction Database and discovered that there are no FDA-approved drugs for CCNB1 and CDCA8, highlighting a promising area for future research. Taken together, our results will be of immense importance in addressing the intricacies of TNBC.