Huang Shang-Yi, Lin Hsiu-Hsia, Yao Ming, Tang Jih-Luh, Wu Shang-Ju, Hou Hsin-An, Chou Wen-Chien, Chou Sheng-Chieh, Hsu Szu-Chun, Ko Bor-Sheng, Lu Hsiao-Yun, Tsay Woei, Tien Hwei-Fang
Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
Department of Laboratory Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
PLoS One. 2015 Sep 17;10(9):e0137552. doi: 10.1371/journal.pone.0137552. eCollection 2015.
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.
骨髓瘤细胞的生长依赖于由基质细胞、分泌的细胞因子和细胞外基质（ECM）组成的骨髓（BM）基质。核心蛋白聚糖是ECM中一种富含亮氨酸的小蛋白聚糖，是一种信号配体和天然抗肿瘤剂。然而，核心蛋白聚糖在骨髓瘤患者中的作用尚不清楚。我们基于121例新诊断骨髓瘤患者的临床特征和治疗反应，评估了通过酶联免疫吸附测定法检测的BM血浆中核心蛋白聚糖水平之间的相关性。患者组和正常对照组的核心蛋白聚糖水平中位数分别为12.31 ng/mL[标准差（SD），7.50 ng/mL；范围，2.45至44.46 ng/mL]和10.31 ng/mL（SD，2.42 ng/mL；范围，4.85 - 15.14 ng/mL）（P < 0.001）。以15.15 ng/mL为临界值，46例患者（38%）表现出较高的核心蛋白聚糖水平（H - DCN），而其他患者表现出正常至较低的核心蛋白聚糖水平（NL - DCN）。除了H - DCN组的中位年龄显著低于NL - DCN组（分别为60.6±14.0岁和65.8±12.2岁；P = 0.034）外，两组之间没有差异。然而，在79例接受基于新型药物诱导治疗的患者中，H - DCN组的总体缓解率显著高于NL - DCN组（分别为97%和63%；P < 0.001），缓解深度也是如此（P = 0.008），而在仅接受化疗药物治疗的患者中未观察到这些情况。H - DCN组的无进展生存期（PFS）显著长于NL - DCN组（分别为未达到和19.5个月；P = 0.0003）。多变量分析表明，H - DCN作为一个显著独立的因素，与更好的治疗反应相关（优势比，20.014；95%置信区间，2.187 - 183.150；P = 0.008）和更长的PFS（风险比，0.135；95%置信区间，0.051 - 0.361；P < 0.001）。这些发现揭示了核心蛋白聚糖在骨髓瘤中的潜在作用，并为进一步研究核心蛋白聚糖与靶向BM基质的新型药物之间可能的协同抗骨髓瘤作用提供了基础。
