Discovery-based protein expression profiling identifies distinct subgroups and pathways in leiomyosarcomas

Mol Cancer Res. 2014 Dec;12(12):1729-39. doi: 10.1158/1541-7786.MCR-14-0072. Epub 2014 Jul 28.

Abstract

Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A substantial portion of these tumors exhibits complex karyotypes and lack characterized chromosomal aberrations. Owing to such properties, both histopathologic and molecular classification of these tumors has been a significant challenge. This study examines the protein expression of a large number of human STS, including subtype heterogeneity, using two-dimensional gel proteomics. In addition, detailed proteome profiles of a subset of pleomorphic STS specimens using an in-depth mass-spectrometry approach identified subgroups within the leiomyosarcomas with distinct protein expression patterns. Pathways analysis indicates that key biologic nodes like apoptosis, cytoskeleton remodeling, and telomere regulation are differentially regulated among these subgroups. Finally, investigating the similarities between protein expression of leiomyosarcomas and undifferentiated pleomorphic sarcomas (UPS) revealed similar protein expression profiles for these tumors, in comparison with pleomorphic leiomyosarcomas.

Implications: These results suggest that UPS tumors share a similar lineage as leiomyosarcomas and are likely to originate from different stages of differentiation from mesenchymal stem cells to smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Cytoskeleton / metabolism
  • Extremities / pathology*
  • Gene Expression Profiling / methods*
  • Gene Regulatory Networks
  • Humans
  • Leiomyosarcoma / metabolism*
  • Leiomyosarcoma / pathology*
  • Mass Spectrometry
  • Middle Aged
  • Proteomics / methods*
  • Signal Transduction*
  • Telomere Homeostasis
  • Thoracic Wall / pathology*