Multi-omics data integration reveals correlated regulatory features of triple negative breast cancer
| Autor: | Allen Gies, Jordan T. Bird, Duah Alkam, Kevin Chappell, Stephanie D. Byrum, Sayem Miah, Kanishka Manna, Christopher E. Randolph, Matthew D. Thompson, Lindsey Hazeslip, Charity L. Washam, Maroof K. Zafar, Alicia K. Byrd, Stefan Graw |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Proteomics Phosphoproteomics Wnt signaling pathway Triple Negative Breast Neoplasms Biology Biochemistry Article 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Cell Line Tumor DNA methylation Genetics biology.protein Cancer research PTEN Humans Molecular Biology Protein kinase B Triple-negative breast cancer PI3K/AKT/mTOR pathway Signal Transduction |
| Zdroj: | Mol Omics |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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