title: 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.
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.
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Hsiu-Hsia
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.affiliation: Department of Laboratory Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Sheng-Chieh
authors.initials: SC
authors.lastname: Chou
authors.affiliation: Department of Laboratory Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Hsiao-Yun
authors.initials: HY
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.affiliation: Department of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D058575:Decorin / Q000378:metabolism*; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; C546878:DCN protein, human; D058575:Decorin