Investigating the prognosis gene profile of triple-negative breast cancer

Abstract

Background: Current therapeutic strategies have poor effects in triple-negative breast cancer (TNBC) patients due to lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression. Identification of novel genes of TNBC prognosis aids in the development of effective treatment strategies. Aim: We aim at explore key genes related to TNBC recurrence. Methods: RNAseq and clinical characteristics data were derived from The Cancer Genome Atlas Breast Invasive Carcinoma project. Ninety-seven TNBC patients were included. We used DESeq2 and Cox regression to identify significant genes to TNBC recurrence. Pathway enrichment analysis and protein–protein interaction plot were conducted to understand the functions of target genes. Results: We discovered top nine important genes for TNBC recurrence. Lower mRNA expression of potassium voltage-gated channel subfamily Q member 5, H3 clustered histone 10, and ADP-ribosylation factor-like protein 17 and higher mRNA expression of synuclein beta, interleukin 6 (IL-6), casein kappa, RHOC, phosphodiesterase 8B, and laminin subunit alpha 3 (LAMA3) were associated with higher risk of recurrence. IL-6, LAMA3, and Ras homolog family member V (RHOV) genes out of nine candidate genes can make the best prediction of TNBC recurrence (area under receiver operating characteristic curve: 0.95, sensitivity: 0.89 and specificity: 0.97). The top three significant Gene Ontology (GO) pathways are nucleosome, ion gated channel activity, and epidermis development. Significant GO pathways can be categorized into four functions: cell–cell adhesion, cell transportation, cell proliferation, ion channel and transporter, and immune. Conclusion: We discovered that the gene set of IL6, LAMA3, and RHOV can accurately predict TNBC recurrence. These genes warrant further study to confirm their causal association with TNBC prognosis and possible treatment targets.