Pan-cancer proteomic map of 949 human cell lines

Emanuel Gonçalves1, Rebecca C Poulos2, Zhaoxiang Cai2

  • 1Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK; Instituto Superior Técnico (IST), Universidade de Lisboa, 1049-001 Lisboa, Portugal; INESC-ID, 1000-029 Lisboa, Portugal.

Cancer Cell
|July 15, 2022
PubMed

Insights

This study analyzed proteomes from 949 cancer cell lines, identifying thousands of protein biomarkers for cancer vulnerabilities. Proteomic data offers unique insights into disease biology and drug response prediction.

Area of Science:

  • Proteomics
  • Cancer Biology
  • Biomarker Discovery

Background:

  • Genomic and transcriptomic data have limitations in revealing disease biology.
  • Large-scale proteomic datasets are scarce, hindering cancer biomarker identification.

Purpose of the Study:

  • To analyze proteomes from a large cohort of cancer cell lines to identify novel cancer biomarkers.
  • To explore the utility of proteomic data in predicting drug response and cancer vulnerabilities.
  • To create a comprehensive proteomic resource for cancer research.

Main Methods:

  • Mass spectrometry-based proteomic analysis of 949 cancer cell lines across 28 tissue types.
  • Quantification of 8,498 proteins, capturing cell-type specificity and post-transcriptional modifications.
  • Integration of multi-omics, drug response, and CRISPR-Cas9 screens with a deep learning pipeline.

Main Results:

  • Identification of thousands of protein biomarkers associated with cancer vulnerabilities, many not significant at the transcript level.
  • Proteome demonstrated similar predictive power for drug response as the transcriptome.
  • Downsampling proteomic data to 1,500 proteins minimally impacted predictive power, indicating robust protein network co-regulation.

Conclusions:

  • Proteomic analysis provides crucial insights into cancer biology and identifies novel biomarkers.
  • The ProCan-DepMapSanger resource offers a valuable tool for cancer research and biomarker discovery.
  • Protein networks are highly interconnected, allowing for robust predictions even with reduced data sets.

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