Membrane protein-regulated networks across human cancers

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Chun-Yu Lin1,2, Chia-Hwa Lee3,4,5, Yi-Hsuan Chuang1

  • 1Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 300, Taiwan.

Nature Communications
|July 18, 2019
PubMed

Insights

This study introduces CaMPNets, a resource detailing 63,746 protein-protein interactions for 1962 membrane proteins across 15 cancers. It aids in discovering prognostic biomarkers and therapeutic targets by linking membrane protein networks to clinical outcomes.

Area of Science:

  • Oncology
  • Proteomics
  • Bioinformatics

Background:

  • Membrane proteins (MPs) and their pathways are key cancer hallmarks, but analyzing their interactions and downstream effects in malignancies is difficult.
  • Understanding these interactions is crucial for identifying new cancer biomarkers and therapeutic targets.

Purpose of the Study:

  • To develop a systematically integrated method for generating a comprehensive resource of cancer membrane protein-regulated networks (CaMPNets).
  • To link membrane protein interactions, genomics, and clinical outcomes to illuminate cancer-wide landscapes and prognostic heterogeneity.

Main Methods:

  • Integrated analysis of expression profiles from 5922 tumors across 15 human cancers.
  • Generated a resource of 63,746 high-confidence protein-protein interactions (PPIs) for 1962 membrane proteins (MPs).
  • Analyzed CaMPNets to link MP partner communities and pathways for biomarker and target identification.

Main Results:

  • The CaMPNets resource contains 63,746 high-confidence PPIs for 1962 MPs across 15 cancer types.
  • Comprehensive analysis identified MP-based gene sets linked to prognostic biomarkers and druggable targets.
  • Identified CHRNA9 as a potential therapeutic target with bupropion as an anti-metastasis agent for nicotine-induced breast cancer.

Conclusions:

  • CaMPNets provides a valuable resource for systematically integrating MP interactions, genomics, and clinical data in cancer research.
  • This resource facilitates the discovery of novel prognostic biomarkers and therapeutic strategies by illuminating cancer-wide networks and tumor heterogeneity.
  • The study highlights the potential of targeting specific MPs, like CHRNA9, and repurposing existing drugs, such as bupropion, for cancer treatment.

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