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iTRAQ-Based Quantitative Proteomic Analysis Strengthens Transcriptomic Subtyping of Triple-Negative Breast Cancer

Pascal Jézéquel1,2,3,4, Catherine Guette4,5, Hamza Lasla1,4

  • 1Unité de Bioinfomique, Institut de Cancérologie de l'Ouest, Bd Jacques Monod, 44805, Saint Herblain Cedex, France.

Proteomics
|April 6, 2019
PubMed

Insights

This study identified three molecular subtypes of triple-negative breast cancer (TNBC) using transcriptomics, paving the way for targeted therapies. Proteomics data, when integrated, helped characterize these subtypes, offering a promising approach for precision medicine.

Area of Science:

  • Oncology
  • Genomics
  • Proteomics

Background:

  • Triple-negative breast cancer (TNBC) presents significant heterogeneity, hindering effective precision treatment.
  • Lack of targeted therapies underscores the need for molecular subtyping and pathway identification in TNBC.

Purpose of the Study:

  • To define clinically relevant TNBC subtypes using integrated proteomics and transcriptomics data.
  • To identify robust molecular classifications for optimizing TNBC patient care.

Main Methods:

  • Unsupervised analysis of transcriptomics and proteomics data from 83 TNBC tumors.
  • Transcriptomics data identified three distinct TNBC subtypes: molecular apocrine (C1), basal-like immune-suppressed (C2), and basal-like immune response (C3).
  • Supervised analysis of proteomics data, guided by transcriptomic subtyping, identified differentially expressed proteins characterizing each subtype.

Main Results:

  • Transcriptomics robustly identified three TNBC subtypes (C1, C2, C3), while unsupervised proteomics did not.
  • Proteomics revealed 30 differentially expressed proteins linked to subtype characteristics: luminal/androgen-regulated (C1), basal/invasion/ECM (C2), and basal/immune response (C3).
  • Integration of transcriptomics and proteomics strengthened TNBC subtyping.

Conclusions:

  • Transcriptomics provides a robust foundation for TNBC molecular subtyping.
  • Integrated multi-omics analysis, particularly proteomics guided by transcriptomics, enhances the characterization of TNBC subtypes.
  • This approach holds promise for advancing precision medicine in TNBC by identifying specific molecular targets and pathways.
Keywords:
integrated analysisproteomicssubtypingtranscriptomicstriple-negative breast cancer

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