Pan-cancer proteogenomic investigations identify post-transcriptional kinase targets [electronic resource]

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 611.018 Cytology and histology

Thông tin xuất bản: Richland, Wash. : Oak Ridge, Tenn. : Pacific Northwest National Laboratory (U.S.) ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2021

Mô tả vật lý: Size: Article No. 1112 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 259634

Identifying genomic alterations of cancer proteins has guided the development of targeted therapies, but proteomic analyses are required to validate and reveal new treatment opportunities. Herein, we develop a new algorithm, OPPTI, to discover overexpressed kinase proteins across 10 cancer types using global mass spectrometry proteomics data of 1,071 cases. OPPTI outperforms existing methods by leveraging multiple co-expressed markers to identify targets overexpressed in a subset of tumors. OPPTI-identified overexpression of ERBB2 and EGFR proteins correlates with genomic amplifications, while CDK4/6, PDK1, and MET protein overexpression frequently occur without corresponding DNA- and RNA-level alterations. Analyzing CRISPR screen data, we confirm expression-driven dependencies of multiple currently-druggable and new target kinases whose expressions are validated by immunochemistry. Identified kinases are further associated with up-regulated phosphorylation levels of corresponding signaling pathways. Collectively, our results reveal protein-level aberrations?sometimes not observed by genomics?represent cancer vulnerabilities that may be targeted in precision oncology.
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