Multi-omics data integration reveals correlated regulatory features of triple negative breast cancer
Triple negative breast cancer (TNBC) is an aggressive type of breast cancer with very little treatment options. TNBC is very heterogeneous with large alterations in the genomic, transcriptomic, and proteomic landscapes leading to various subtypes with differing responses to therapeutic treatments. W...
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Published in | Molecular omics Vol. 17; no. 5; pp. 677 - 691 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
The Royal Society of Chemistry
11.10.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Triple negative breast cancer (TNBC) is an aggressive type of breast cancer with very little treatment options. TNBC is very heterogeneous with large alterations in the genomic, transcriptomic, and proteomic landscapes leading to various subtypes with differing responses to therapeutic treatments. We applied a multi-omics data integration method to evaluate the correlation of important regulatory features in TNBC BRCA1 wild-type MDA-MB-231 and TNBC BRCA1 5382insC mutated HCC1937 cells compared with non-tumorigenic epithelial breast MCF10A cells. The data includes DNA methylation, RNAseq, protein, phosphoproteomics, and histone post-translational modification. Data integration methods identified regulatory features from each omics method that had greater than 80% positive correlation within each TNBC subtype. Key regulatory features at each omics level were identified distinguishing the three cell lines and were involved in important cancer related pathways such as TGFβ signaling, PI3K/AKT/mTOR, and Wnt/beta-catenin signaling. We observed overexpression of PTEN, which antagonizes the PI3K/AKT/mTOR pathway, and MYC, which downregulates the same pathway in the HCC1937 cells relative to the MDA-MB-231 cells. The PI3K/AKT/mTOR and Wnt/beta-catenin pathways are both downregulated in HCC1937 cells relative to MDA-MB-231 cells, which likely explains the divergent sensitivities of these cell lines to inhibitors of downstream signaling pathways. The DNA methylation and RNAseq data is freely available
via
GEO GSE171958 and the proteomics data is available
via
the ProteomeXchange PXD025238.
Multi-omics data integration of triple negative breast cancer (TNBC) provides insight into biological pathways. |
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Bibliography: | Electronic supplementary information (ESI) available: Supplemental file 1: Illumina EPIC beadChip array DNA methylation normalized values and statistical results. Supplemental file 2: RNA-seq normalized counts and statistical results. Supplemental file 3: Protein normalized MS3 intensities and statistical results. Supplemental file 4: Phosphopeptide normalized MS3 intensities and statistical results. Supplemental file 5: Histone post-translational modifications normalized MS1 intensities. Supplemental file 6: DNA methylation of promoter regions and RNAseq gene expression common features and correlation results from Supplemental file 7: RNAseq and protein common features and correlation results. Supplemental file 8: Protein and phosphorylated peptide features and correlation results. See DOI Fig. 3 10.1039/d1mo00117e ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors have contributed equally to this work. |
ISSN: | 2515-4184 2515-4184 |
DOI: | 10.1039/d1mo00117e |