Pan-cancer proteogenomic investigations identify post-transcriptional kinase targets

Abdulkadir Elmas, Serena Tharakan, Suraj Jaladanki, Matthew D. Galsky, Tao Liu, Kuan lin Huang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish
Article number1112
JournalCommunications Biology
Issue number1
StatePublished - Dec 2021


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