TY - JOUR
T1 - Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker of myxofibrosarcoma invasion identified by global protein expression profiling
AU - Kikuta, Kazutaka
AU - Kubota, Daisuke
AU - Yoshida, Akihiko
AU - Qiao, Zhiwei
AU - Morioka, Hideo
AU - Nakamura, Masaya
AU - Matsumoto, Morio
AU - Chuman, Hirokazu
AU - Kawai, Akira
AU - Kondo, Tadashi
N1 - Funding Information:
This research was supported by the Practical Research for Innovative Cancer Control Program from the Japan Agency for Medical Research and Development (AMED) (grant number 15ck0106089h0002) and JSPS KAKENHI grant number JP15K20017.
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
KW - Biomarker
KW - DCBLD2
KW - Invasion
KW - Myxofibrosarcoma
KW - Two-dimensional difference gel electrophoresis
UR - http://www.scopus.com/inward/record.url?scp=85021684704&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021684704&partnerID=8YFLogxK
U2 - 10.1016/j.bbapap.2017.06.023
DO - 10.1016/j.bbapap.2017.06.023
M3 - Article
C2 - 28668639
AN - SCOPUS:85021684704
VL - 1865
SP - 1160
EP - 1166
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
SN - 1570-9639
IS - 9
ER -