Proteomic profile of melanoma cell-derived small extracellular vesicles in patients' plasma: a potential correlate of melanoma progression

J Extracell Vesicles. 2021 Feb;10(4):e12063. doi: 10.1002/jev2.12063. Epub 2021 Feb 11.

Abstract

Molecular profiling of small extracellular vesicles (sEV) isolated from plasma of cancer patients emerges as promising strategy for biomarkers discovery. We investigated the proteomic profiles of sEV immunoselected using anti-CSPG4 antibodies from 15 melanoma patients' plasma. The proteomes of sEV separated into melanoma cell-derived (MTEX) and non-malignant cell-derived (NMTEX) were compared using high-resolution mass spectrometry. Paired analysis identified the MTEX-associated profile of 16 proteins that discriminated MTEX from NMETEX. We also identified the MTEX profile that discriminated between seven patients with no evidence of melanoma (NED) after therapy and eight with progressive disease (PD). Among 75 MTEX proteins overexpressed in PD patients, PDCD6IP (ALIX) had the highest discriminating value, while CNTN1 (contactin-1) was upregulated only in MTEX of NED patients. This is the first report documenting that proteomes of tumour-derived sEV in patients' plasma discriminate cancer from non-cancer and identify proteins with potential to serve as prognostic biomarkers in melanoma.

Keywords: high‐resolution mass spectrometry (HRMS); melanoma cell‐derived exosomes (MTEX); proteomics; small extracellular vesicles (sEV); tumour‐derived exosomes (TEX).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Chondroitin Sulfate Proteoglycans / immunology
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Contactin 1 / metabolism
  • Disease Progression
  • Exosomes / chemistry
  • Exosomes / metabolism*
  • Extracellular Vesicles / chemistry
  • Extracellular Vesicles / metabolism*
  • Female
  • Humans
  • Male
  • Mass Spectrometry
  • Melanoma / chemistry
  • Melanoma / metabolism*
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Middle Aged
  • Plasma / chemistry
  • Plasma / metabolism*
  • Proteins / metabolism
  • Proteome / metabolism*

Substances

  • Biomarkers, Tumor
  • CNTN1 protein, human
  • CSPG4 protein, human
  • Chondroitin Sulfate Proteoglycans
  • Contactin 1
  • Membrane Proteins
  • Proteins
  • Proteome