Molecular signatures of tumor progression in myxoid liposarcoma identified by N-glycan mass spectrometry imaging

Lab Invest. 2020 Sep;100(9):1252-1261. doi: 10.1038/s41374-020-0435-2. Epub 2020 Apr 27.


Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, accounting for ~6% of all sarcomas. MLS is characterized by a pathognomonic FUS-DDIT3, or rarely EWSR1-DDIT3, gene fusion. The presence of ≥5% hypercellular round cell areas is associated with a worse prognosis for the patient and is considered high grade. The prognostic significance of areas with moderately increased cellularity (intermediate) is currently unknown. Here we have applied matrix-assisted laser desorption/ionization mass spectrometry imaging to analyze the spatial distribution of N-linked glycans on an MLS microarray in order to identify molecular markers for tumor progression. Comparison of the N-glycan profiles revealed that increased relative abundances of high-mannose type glycans were associated with tumor progression. Concomitantly, an increase of the average number of mannoses on high-mannose glycans was observed. Although overall levels of complex-type glycans decreased, an increase of tri- and tetra-antennary N-glycans was observed with morphological tumor progression and increased tumor histological grade. The high abundance of tri-antennary N-glycan species was also associated with poor disease-specific survival. These findings mirror recent observations in colorectal cancer, breast cancer, ovarian cancer, and cholangiocarcinoma, and are in line with a general role of high-mannose glycans and higher-antennary complex-type glycans in cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Liposarcoma, Myxoid / genetics
  • Liposarcoma, Myxoid / metabolism*
  • Liposarcoma, Myxoid / pathology
  • Male
  • Neoplasm Grading
  • Oncogene Proteins, Fusion / genetics
  • Polysaccharides / metabolism*
  • Repressor Proteins / genetics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Tandem Mass Spectrometry / methods*


  • EWSR1-DDIT3 protein, human
  • FUS-DDIT3 fusion protein, human
  • Oncogene Proteins, Fusion
  • Polysaccharides
  • Repressor Proteins