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.
Highlights
Multiple myeloma (MM) is monoclonal plasma cell proliferation in the bone marrow (BM) [1]
In addition to such structural components, subsequent studies have revealed that decorin may sequester multiple growth factors, such as transforming growth factor-β (TGF-β) [11], and may bind to several receptor tyrosine kinases, including epidermal growth factor receptor (EGFR), insulin-like growth factor-I receptor (IGF-IR), and hepatocyte growth factor (HGF) receptor (Met), etc. [8, 11]
This study and consent procedure was approved by the National Taiwan University Hospital Research Ethics Committee (NTUHREC: 201212114RINC), and written informed consent was obtained from all study participants in accordance with the Declaration of Helsinki and kept in their medical records
Summary
Multiple myeloma (MM) is monoclonal plasma cell proliferation in the bone marrow (BM) [1]. The stromal cells and secreted cytokines are known to regulate growth, drug resistance, angiogenesis, and the extramedullary expansion of MCs [4, 5], the role of the ECM remains unclear. Mutations in decorin lead to connective tissue disorders such as congenital stromal corneal dystrophy [9, 10] In addition to such structural components, subsequent studies have revealed that decorin may sequester multiple growth factors, such as transforming growth factor-β (TGF-β) [11], and may bind to several receptor tyrosine kinases, including epidermal growth factor receptor (EGFR), insulin-like growth factor-I receptor (IGF-IR), and hepatocyte growth factor (HGF) receptor (Met), etc. Decorin is being reconsidered as a novel and native signaling ligand rather than a structural protein alone, that contributes to numerous pathophysiological processes, including inhibition of tumor growth, metastasis, and angiogenesis [7, 8]
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