Higher decorin levels in bone marrow plasma are associated with superior treatment response to novel agent-based induction in patients with newly diagnosed myeloma - A retrospective study
Journal
PLoS ONE
Journal Volume
10
Journal Issue
9
Date Issued
2015
Author(s)
Abstract
The growth of myeloma cells depends on bone marrow (BM) stroma consisting of stromal cells, secreted cytokines and the extracellular matrix (ECM). Decorin, a small leucine-rich proteoglycan in the ECM, is a signaling ligand and native anti-tumor agent. However, the role of decorin in patients with myeloma is not clear. We evaluated the correlation between the decorin levels measured by enzyme-linked immunosorbent assay in BM plasma from 121 patients with newly diagnosed myeloma based on their clinical features and treatment response. The median decorin levels in the patients and the normal control group were 12.31 ng/mL [standard deviation (SD), 7.50 ng/mL; range, 2.45 to 44.46 ng/mL] and 10.31 ng/mL (SD, 2.42 ng/mL; range, 4.85-15.14 ng/mL), respectively (P < 0.001). Using 15.15 ng/mL as a cut-off, 46 patients (38%) exhibited higher decorin levels (H-DCN), whereas the other patients exhibited normal to lower decorin levels (NL-DCN). Except for the median age, which was significantly younger in the H-DCN than in the NL-DCN group (60.6±14.0 vs. 65.8±12.2 years, respectively; P = 0.034), there were no differences between the two groups. However, in 79 patients who had received novel agent-based induction, the overall response rate was significantly better in the H-DCN than in the NL-DCN (97 vs. 63%, respectively; P < 0.001), as was the depth of responses (P = 0.008), which were not observed in those who had received chemotherapeutic agents alone. Progression-free survival (PFS) was significantly longer in H-DCN than NL-DCN (not reached vs. 19.5 mo, respectively; P = 0.0003). Multivariate analyses indicated that H-DCN, as a significantly independent factor, was associated with better treatment response (odds ratio, 20.014; 95% CI, 2.187-183.150; P = 0.008) and longer PFS (hazard ratio, 0.135; 95% CI, 0.051- 0.361; P < 0.001). These findings disclose the potential role of decorin in myeloma and provide a basis for further study on possible synergistic anti-myeloma effects between decorin and the novel agents that target BM stroma.
SDGs
Other Subjects
bortezomib; cyclophosphamide; decorin; dexamethasone; doxorubicin; melphalan; prednisolone; thalidomide; vincristine; antineoplastic agent; cytokine; DCN protein, human; decorin; adult; aged; Article; bone marrow; clinical feature; continuous infusion; controlled study; drug megadose; enzyme linked immunosorbent assay; female; human; major clinical study; male; multiple myeloma; overall survival; progression free survival; protein blood level; retrospective study; treatment response; bone marrow cell; cell proliferation; disease free survival; extracellular matrix; induction chemotherapy; metabolism; middle aged; mortality; multiple myeloma; pathology; procedures; secretion (process); treatment outcome; young adult; Adult; Aged; Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Cell Proliferation; Cytokines; Decorin; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix; Female; Humans; Induction Chemotherapy; Male; Middle Aged; Multiple Myeloma; Retrospective Studies; Treatment Outcome; Young Adult
Publisher
Public Library of Science
Type
journal article