Multi-omics data integration reveals correlated regulatory features of triple negative breast cancer.
Multi-omics data integration reveals correlated regulatory features of triple negative breast cancer.
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多组学数据集成揭示了三阴性乳腺癌的相关调控特征。
DOI：
10.1039/d1mo00117e
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发表时间：
2021-10-11
期刊：
影响因子：
2.9
通讯作者：
Byrum SD
中科院分区：
文献类型：
--
作者：
Chappell K;Manna K;Washam CL;Graw S;Alkam D;Thompson MD;Zafar MK;Hazeslip L;Randolph C;Gies A;Bird JT;Byrd AK;Miah S;Byrum SD
三阴性乳腺癌（TNBC）是一种侵袭性类型的乳腺癌，治疗选择很少。TNBC是非常异质的，在基因组、转录组和蛋白质组学景观中具有大的改变，导致对治疗性治疗具有不同反应的各种亚型。我们应用多组学数据整合方法来评估TNBC BRCA 1野生型MDA-MB-231和TNBC BRCA 1 5382 insC突变的HCC 1937细胞与非致瘤性乳腺上皮MCF 10A细胞中重要调控特征的相关性。数据包括DNA甲基化、RNAseq、蛋白质、磷酸化蛋白质组学和组蛋白翻译后修饰。数据整合方法从每种组学方法中鉴定出在每种TNBC亚型内具有大于80%正相关性的调控特征。在每个组学水平的关键调控特征被鉴定为区分三种细胞系，并且参与重要的癌症相关途径，如TGFβ信号传导、PI 3 K/AKT/mTOR和Wnt/β-连环蛋白信号传导。我们观察到PTEN和MYC的过表达，PTEN拮抗PI 3 K/AKT/mTOR通路，MYC相对于MDA-MB-231细胞在HCC 1937细胞中下调相同的通路。与MDA-MB-231细胞相比，HCC 1937细胞中PI 3 K/AKT/mTOR和Wnt/β-连环蛋白通路均下调，这可能解释了这些细胞系对下游信号传导通路抑制剂的不同敏感性。DNA甲基化和RNAseq数据可通过GEO GSE 171958免费获得，蛋白质组学数据可通过ProteomeXchange PXD 025238获得。三阴性乳腺癌（TNBC）的多组学数据整合提供了对生物学途径的深入了解。
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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影响因子：
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作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
三阴性乳腺癌的基因组和转录组景观：亚型和治疗策略
影响因子：
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Schiffer, Mario
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64.8
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Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel