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

Abstract

AbstractMyxoid 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.This study on myxoid liposarcoma, based on mass spectrometry imaging of N-glycans, has revealed that increases in high-mannose-type as well as tri- and tetra-antennary complex-type N-glycans are associated with morphological progression of the disease. The increased abundance of tri-antennary complex-type glycans was also associated with a poor disease-specific survival for the patients.