Metastasis-associated gene signature in primary myxoid liposarcoma identified through a gene expression study

Abstract

Myxoid liposarcoma (MLS) is a rare mesenchymal malignancy with unique extrapulmonary metastatic potential. Although MLS has been associated with specific chromosomal translocations, the factors and pathways regulating metastasis in MLS remain unknown. To identify the molecular mechanisms underlying MLS metastasis, we compared global gene expression profiles of primary tumor tissues from MLS patients with different metastatic statuses using DNA microarray analysis. In total, 393 genes were differentially expressed between the tumors from four patients with metastasis and those from 11 patients without metastasis. Differentially expressed genes were functionally annotated based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Supervised classification based on the 393 genes clearly discriminated samples according to metastatic status. The pathways responsible for metastasis included “focal adhesion,” “pathways in cancer,” “ECM-receptor interaction,” and “tight junction.” The differential expression of alpha-synuclein was confirmed at the protein level; the protein was downregulated in metastatic MLS. Meta-analysis revealed that MLS could be discriminated from the other sarcomas based on the expression of the metastasis-associated genes. The metastasis-associated genes identified in this study are worthwhile further investigation to further our understanding of MLS and are expected to lead to novel clinical applications for MLS.