Abstract
BackgroundThe aim of this study was to identify the key differentially expressed genes (DEGs) and high-risk gene mutations in breast ductal carcinoma in situ (DCIS).MethodsRaw data (GSE36863) were downloaded from the database of Gene Expression Omnibus (GEO), including three DCIS samples (DCIS cell lines MCF10.DCIS, Sum102, and Sum225) and one normal control sample (normal mammary epithelial cell line MCF10A). The DEGs were analyzed using NOIseq and annotated via DAVID. Motif scanning in the promoter region of DEGs was performed via SeqPos. Additionally, single nucleotide variations (SNVs) were identified via GenomeAnalysisTK and SNV risk was assessed via VarioWatch. Mutant genes with a high frequency and risk were validated by RT-PCR analyses.ResultsFinally, 5391, 7073, and 7944 DEGs were identified in DCIS, Sum102, and Sum22 cell lines, respectively, when compared with MCF10A. VENN analysis of the three cell lines revealed 603 upregulated and 1043 downregulated DEGs, including 16 upregulated and 36 downregulated transcription factor (TF) genes. In addition, six TFs each (e.g., E2F1 and CREB1) were found to regulate the core up- and downregulated DEGs, respectively. Furthermore, SNV detection results revealed 1104 (MCF10.DCIS), 2833 (Sum102), and 1132 (Sum22) mutation sites. Four mutant genes (RWDD4, SDHC, SEPT7, and SFN) with high frequency and risk were identified. The results of RT-PCR analysis as well as bioinformatics analysis consistently demonstrated that the expression of RWDD4, SDHC, SEPT7, and SFN was downregulated in the tumor tissues as compared with that in adjacent non-tumor tissues.ConclusionsThe differentially expressed TFs, TFs regulating DEGs (e.g., E2F1 and CREB1), and high-frequency mutant genes (RWDD4, SDHC, SEPT7, and SFN) might play key roles in the pathogenesis of DCIS.
Highlights
The aim of this study was to identify the key differentially expressed genes (DEGs) and high-risk gene mutations in breast ductal carcinoma in situ (DCIS)
Identification of DEGs and functional enrichment analysis As compared with the MCF10A cell line, 5391, 7073, and 7944 DEGs were identified in MCF10.DCIS, Sum102, and Sum22 cell lines, respectively, and the ratios of up- and downregulated DEGs were 0.98, 0.99, and 1.26, respectively, without any significant bias of up- or downregulation
The enrichment of positively regulated tumor necrosis factor production was most significant in Sum102, while the enrichment of second-messenger-mediated signaling was more common in Sum225 and MCF10.DCIS cell lines
Summary
The aim of this study was to identify the key differentially expressed genes (DEGs) and high-risk gene mutations in breast ductal carcinoma in situ (DCIS). Based on RNA-Seq analysis, Tian et al [10] identified differentially expressed transcripts in DCIS models, which are associated with signaling pathways such as cell proliferation, cell-cell adhesion, and cell-cell signaling, and reported that aldehyde dehydrogenase 5A1 (ALDH5A1) may serve as a novel molecular target in DCIS treatment. RNA-Seq data deposited by Kaur et al [11], including three DCIS samples (MCF10.DCIS, Sum102, and Sum22) and one normal control sample (MCF10A), were downloaded to identify the differentially expressed genes (DEGs). Single nucleotide variants (SNVs) in DCIS were identified and annotated These results might improve our understanding of the molecular mechanism underlying DCIS and suggest potential targets for clinical treatment
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