Makale detayı · 2021
Pan-cancer proteogenomic investigations identify post-transcriptional kinase targets
- Yıl
- 2021
- Tür
- article
Veri kaynağı ayrımı
- YÖKSİS YÖKSİS makale kaydı
- YÖKSİS dergi adı COMMUNICATIONS BIOLOGY
- Katalog eşleşmesi (ISSN) Communications Biology
- OpenAlex OpenAlex zenginleştirmesi (özet, atıf, konular)
Özet
OpenAlex · İngilizce
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.
Konular
Atıflar
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18 atıf
OpenAlex cited_by_count (önbellek / veritabanı)
Yerel katalogda bu makaleye atıf yapan 9 yayın (OpenAlex referans eşleşmesi; tam dünya listesi değildir).
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