Article detail · 2021
Pan-cancer proteogenomic investigations identify post-transcriptional kinase targets
- Year
- 2021
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue COMMUNICATIONS BIOLOGY
- Catalog match (ISSN) Communications Biology
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
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.
Topics
Citations
OpenAlex cited_by_count. Not a WoS or Scopus citation count; those sources have no separate column here.
18 citations
OpenAlex cited_by_count (cache / database)
9 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
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- Structural Analysis of Genomic and Proteomic Signatures Reveal Dynamic Expression of Intrinsically Disordered Regions in Breast Cancer and Tissue 2023
- Actionable targets in breast cancer: a multi-omics approach to uncover tumor-specific vulnerabilities 2025
- Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy 2025