Correlations of DKK1 with pathogenesis and prognosis of human multiple myeloma

Article type: Research Article

Authors: Feng, Youfan^a | Zhang, Yuxia^b | Wei, Xiaofang^a | Zhang, Qike^{a; *}

Affiliations: [a] Department of Hematology, Gansu Provincial Hospital, Lanzhou, Gansu, China | [b] Department of Hematology, Huining County People’s Hospital, Baiyin, Gansu, China

Correspondence: [*] Corresponding author: Qike Zhang, Department of Hematology, Gansu Provincial Hospital, 204 Donggang West Road, Chengguan District, Lanzhou, Gansu 730000, China. Tel.: +86 931 8281114; Fax: +86 931 8281114; E-mail: [email protected].

Abstract: OBJECTIVE: Human multiple myeloma (MM) is a kind of common tumor in middle-aged and elderly people, in which the osteolytic lesion is formed mainly through inhibiting osteoblast (OB) differentiation and promoting osteoclast (OC) differentiation. Dickkopf-1 (DKK1) is a soluble Wnt inhibitor, which has an important correlation with the pathogenesis of human MM. Therefore, the correlations of DKK1 with pathogenesis and prognosis of human MM were investigated in this study. METHODS: The DKK1 expression in tissues and serum of myeloma patients was detected via immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Correlation between DKK1 expression and survival time of patients was analyzed via Kaplan-Meier analysis. To further study the mechanism of DKK1 expression in pathogenesis and prognosis of human MM, MM cells were treated with DKK1 neutralizing antibody (BHQ880) or transfected with DKK1-small-interfering ribonucleic acid (siRNA) to study its effects on OB differentiation, osteocalcin level, β-catenin and interleukin-6 (IL-6) secretion. Moreover, the effect of DKK1-siRNA transfection on the activity of U266 cells was detected via methyl thiazolyl tetrazolium (MTT) assay. RESULTS: The DKK1 expression in tissues and serum of myeloma patients was significantly higher than that in control group (p< 0.01). In terms of survival time, the median survival time (45 months) in patients with low DKK1 expression was significantly longer than that in patients with high DKK1 expression (only 22 months). The DKK1 neutralizing antibody (BHQ880) and DKK1-siRNA significantly reduced the DKK1 level in MM cells, promoted the OB differentiation, increased the osteocalcin deposition, promoted the β-catenin expression and decreased the IL-6 expression and β-catenin phosphorylation. DKK1-siRNA could also reduce the proliferative activity of MM cells. CONCLUSION: DKK1 is closely related to the pathogenesis and prognosis of human MM, which might be a potential biomarker for the diagnosis of MM.

Keywords: DKK1, human multiple myeloma, pathogenesis, prognosis

DOI: 10.3233/CBM-181909

Journal: Cancer Biomarkers, vol. 24, no. 2, pp. 195-201, 2019