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Published on: March 30, 2019
RNA-sequencing and microarray data mining revealing: the aberrantly expressed mRNAs were related with a poor outcome
Hongjun Fei1, Songchang Chen1, Chenming Xu1
1Department of Reproductive Genetics, Shanghai Key Laboratory of Embryo Original Diseases, International Peace Maternity and Child Health Hospital, Shanghai Municipal Key Clinical Specialty, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Background:
Triple 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.
Methods:
We 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.
Results:
Of 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.
Conclusions:
From all above results, we speculate that NAT1, GATA3 and SCUBE2 play a vital role in TNBC.
Insights
This study identifies N-acetyltransferase 1 (NAT1), GATA binding protein 3 (GATA3), and signal peptide CUB domain containing 2 (SCUBE2) as key genes in triple-negative breast cancer (TNBC). Their expression is linked to patient prognosis, suggesting potential therapeutic targets for TNBC.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Triple-negative breast cancer (TNBC) lacks specific molecular targets and targeted therapies, posing a clinical challenge.
- Current American Society of Clinical Oncology guidelines offer limited specific approaches for TNBC management.
Purpose of the Study:
- To identify novel molecular targets and potential therapeutic strategies for triple-negative breast cancer.
- To analyze differentially expressed genes (DEGs) in TNBC using bioinformatics approaches.
Main Methods:
- RNA-sequencing data from Gene Expression Omnibus (GEO) database was analyzed to identify aberrantly expressed mRNAs in TNBC.
- Differentially expressed genes (DEGs) were rigorously analyzed using combined bioinformatics approaches, including hierarchical clustering, functional and pathway enrichment, and protein-protein interaction (PPI) network construction.
- Co-expression and co-occurrence analyses were performed to investigate the relationships between candidate genes and N-acetyltransferase 1 (NAT1).
Main Results:
- Out of 21,755 genes analyzed across 472 TNBC cases, 159 mRNAs were identified as DEGs.
- N-acetyltransferase 1 (NAT1) exhibited the most significant expression change among all DEGs.
- Three hub genes, desmoglein 3 (DSG3), FAM83D, and GATA3, were identified through PPI network analysis. NAT1 co-expression analysis revealed significant associations with GATA3, TFF3, FOXA1, SCUBE2, and GPR160. GATA3 and SCUBE2 showed a tendency for co-occurrence with NAT1 in TNBC.
- Survival analysis indicated that the expression of NAT1, GATA3, and SCUBE2 is significantly correlated with patient prognosis.
Conclusions:
- N-acetyltransferase 1 (NAT1), GATA binding protein 3 (GATA3), and signal peptide CUB domain containing 2 (SCUBE2) are identified as key genes potentially playing vital roles in triple-negative breast cancer.
- These genes represent promising candidates for further investigation as potential biomarkers and therapeutic targets for TNBC.
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