Integrative bioinformatics and RNA sequencing based methodology results in the exploration of breast invasive carcinoma biomarkers.

Background: Previously reported breast invasive carcinoma (BRIC) biomarkers have compromised utility because of their heterogeneity-specific behaviors. The goal of this study was to find BRIC biomarkers that could be used in spite of the heterogeneity barrier.

Methods: Previously reported BRIC-linked hub genes were obtained from the literature via a search technique. A protein-protein interaction (PPI) network of the extracted hub genes was constructed, visualized, and analyzed to explore the top six real hub genes. Following this, real hub genes' expression profiling was carried out using various TCGA data sources and RNA sequencing (RNA-seq) of BT 20 and HMEC cell lines to uncover the tumor-driver roles of the real hub genes.

Results: In total, 124 BRIC-linked hub genes were collected from the literature via the search technique. From these collected hub genes, a total of 6 genes, including Centrosomal protein of 55 kDa (CEP55), Kinesin Family Member 2C (KIF2C), kinesin family member 20A (KIF20A), Ribonucleotide Reductase Regulatory Subunit M2 (RRM2), Aurora A Kinase (AURKA), and Protein Regulator of cytokinesis 1 (PRC1) were determined to be the real hub genes. Via expression profiling and validation analyses, we documented the overexpression of CEP55, KIF2C, KIF20A, RRM2, AURKA, and PRC1 real hub genes in BRIC patients with different clinical variables. Further correlational analyses showed diverse associations among real hub genes' expression and other important parameters, including promoter methylation status, genetic alteration, overall survival (OS), relapse-free survival (RFS), tumor purity, CD8+ T, CD4+ T immune cell infiltration, and different mutant genes across BRIC samples. Finally, in this work, we investigated several transcription factors (TFS), microRNAs, and therapeutic medicines related to the real hub genes that have great therapeutic potential.

Conclusion: In conclusion, we discovered six real hub genes, which may be employed as novel potential biomarkers for BRIC patients with different clinical parameters.