Myxofibrosarcoma (MFS) is a mesenchymal
malignancy characterized by frequent recurrence even after radical wide resection. To optimize
therapy for MFS patients, we aimed to identify candidate tissue
biomarkers of MFS invasion potential. Invasion characteristics of MFS were evaluated by magnetic resonance imaging and
protein expression profiling of primary
tumor tissues performed using two-dimensional difference gel electrophoresis (2D-DIGE).
Protein expression profiles were compared between invasive and non-invasive
tumors surgically resected from 11 patients. Among the 3453
protein spots observed, 59 demonstrated statistically significant difference in intensity (≥2-fold) between invasive and non-invasive
tumors (p<0.01 by Wilkoxon test), and were identified by mass spectrometry as 47 individual
proteins. Among them, we further focused on
discoidin, CUB and LCCL domain-containing
protein 2 (DCBLD2), a
receptor tyrosine kinase with aberrant expression in malignant
tumors. Immunohistochemistry analysis of 21 additional MFS cases revealed that higher DCBLD2 expression was significantly associated with invasive properties of
tumor cells. DCBLD2 sensitivity and specificity, and positive and negative predictive values for MFS invasion were 69.2%, 87.5%, 90%, and 63.6%, respectively. The expression level of DCBLD2 was consistent in different portions of
tumor tissues. Thus, DCBLD2 expression can be a useful
biomarker to evaluate invasive properties of MFS. Further validation studies based on multi-institutional collaboration and comprehensive analysis of DCBLD2 biological functions in MFS are required to confirm its prognostic utility for clinical application.