RNA-sequencing and microarray data mining revealing: the aberrantly expressed mRNAs were related with a poor outcome in the triple negative breast cancer patients.

Abstract

BackgroundTriple negative breast cancer (TNBC) account for about 20% of breast carcinomas and the American society of clinical oncology guidelines does not specify approaches for TNBC patients since lack of specific driver molecules and targeted drugs.MethodsWe filtered out the aberrantly expressed mRNAs on the basis of RNA-seq data deposited in the Gene Expression Omnibus database, and verified and deeply analyzed screened differentially expressed genes (DEGs) using a combined bioinformatics approach.ResultsOf 21,755 genes with 472 TNBC cases from 3 independent laboratories, 159 mRNAs were identified as DEGs. To verify our results, we assessed the expression levels of top 8 DEGs in Oncomine database. The hierarchical clustering analysis, functional and pathway enrichment analysis were carried out for all DEGs. The results reveal that N-acetyltransferase 1 (NAT1) is most obvious of expression change’s gene. Protein-protein interaction (PPI) network construction of 159 DEGs selected 3 hub genes: desmoglein 3 (DSG3), family with sequence similarity 83 member D (FAM83D) and GATA binding protein 3 (GATA3). For further analysis of the potential role of NAT1 in TNBC, the co-expression profiles of NAT1 in BC were made out, and we found that there are 5 genes [GATA3, trefoil factor 3 (TFF3), forkhead box A1 (FOXA1), signal peptide, CUB domain and EGF like domain containing 2 (SCUBE2), G protein-coupled receptor 160 (GPR160)] which co-expressed with NAT1 also were DEGs that we screened out before. Co-occurrence analysis confirmed that same as DEGs, GATA3 and SCUBE2 co-expressed with NAT1, and had a tendency towards a co-occurrence with NAT1 in TNBC. The survival curves showed that NAT1, GATA3 and SCUBE2 expression are significantly related with prognosis.ConclusionsFrom all above results, we speculate that NAT1, GATA3 and SCUBE2 play a vital role in TNBC.