Novel Proteome Extraction Method Illustrates a Conserved Immunological Signature of MSI-H Colorectal Tumors

Mol Cell Proteomics. 2020 Oct;19(10):1619-1631. doi: 10.1074/mcp.RA120.002152. Epub 2020 Jul 8.

Abstract

Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon-γ induces a similar signature in vitro We identified 10 different temporal protein expression patterns, classifying the Interferon-γ protein temporal regulation in CRC. Our data sheds light on the changes that tumor cells undergo under long-term immunological pressure in vivo, the importance of STAT proteins in specific biological scenarios. The data generated could help find novel clinical biomarkers and therapeutic approaches.

Keywords: Clinical proteomics; colorectal cancer; immunohistochemistry; immunology; inflammatory response; label-free quantification; molecular biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology*
  • Formaldehyde / chemistry
  • Humans
  • Interferon-gamma / pharmacology
  • Microsatellite Instability*
  • Paraffin Embedding
  • Proteome / metabolism*
  • Proteomics / methods*
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Tissue Fixation

Substances

  • Proteome
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Formaldehyde
  • Interferon-gamma