Study Finds Decorin May Have Protective Effect in Multiple Myeloma

Decorin, a highly conserved, class 1 small leucine-rich repeat proteoglycan expressed in the extracellular matrix, was found to be highly correlated with hepatocyte growth factor (HGF) levels in bone marrow plasma among patients with newly diagnosed multiple myeloma (MM), investigators concluded.

Results of the recent study, published in the Journal of the Formosan Medical Association, suggested that decorin in bone marrow mesenchymal stem cells (BMMSCs) may have a protective effect in patients with MM who have low HGF levels.

“These data indicate that decorin levels increase during disease progression as a result of increased collagen breakdown and higher HGF levels, as well as relatively competent BMMSCs,” wrote the investigators.

Decorin binds to tyrosine kinase receptors including HGF receptor mesenchymal-epithelial transition factor (MET), which promotes MM progression when signaled. Patients with high levels of MET were at a higher risk of having advanced disease and a poorer prognosis. Additionally, high HGF levels are associated with adverse outcomes in patients with MM.

The only known ligands for MET are HGF and decorin. Although HGF may promote cancer progression, decorin may have tumor suppressive activities and has been shown to inhibit myeloma cell growth through downregulation of MET. However, more research is needed to determine whether decorin and HGF levels are correlated with clinical features in newly diagnosed MM.

Between July 1998 and March 2014, the investigators assessed decorin and HGF levels in bone marrow samples collected from 270 patients with newly diagnosed MM at the National Taiwan University Hospital in Taipei, Taiwan.

The patients were divided into 2 groups according to decorin levels, with the high decorin group accounting for the top 25% of the data and the low decorin group comprising the bottom 25% of the data. Patients in the high decorin group exhibited lower hemoglobin levels, increased bone marrow plasma cell infiltration, increases in cytogenetic abnormalities, a higher prevalence of vertebral and nonvertebral fractures, higher calcium levels, and longer activated partial thromboplastin times.

The patients were also split into a high HGF group and a low HGF group. A positive correlation was observed between decorin and HGF levels, and HGF levels were higher in the high decorin group.

Additionally, patients in the low HGF group with median decorin levels of 12.95 ng/ml or greater had a better overall response rate to MM treatments compared with those who had decorin levels of less than 12.95 ng/ml (90.5% vs 54.5%; P = .015). A multivariate analysis confirmed that in the low HGF group, a decorin level of 12.95 ng/ml or greater was an independent factor for improved overall response rates (odds ratio, 11.68; P = .011) and overall survival (hazard ratio, 0.127; P = .02) with regard to receiving MM therapy.

The investigators hypothesized, based on their results, that decorin may convert immune reactions into an apoptotic and inflammatory response that exerts antitumor effects. Furthermore, they said the positive correlation between high decorin levels and advanced-stage disease could have several explanations, including that the half-life of decorin may be prolonged when there is an abundance of HGF in a patient’s bone marrow microenvironment, especially because HGF and decorin compete with each other for MET binding.

“Although we identified a correlation between decorin and HGF levels, it was relatively weak, suggesting other factors might contribute to the increase in decorin levels in patients with advanced disease,” wrote the investigators.

The study had some limitations, including a small sample size, the retrospective design, use of archived patient samples, and variability in induction therapy regimens among the analyzed patients.

Reference

Huang S, Lin H, Yao M, et al. Bone marrow plasma level of decorin may be associated with improved treatment outcomes in a subset of multiple myeloma patients. J Formos Med Assoc. 2022;121:643-651.doi: 10.1016/j.jfma.2021.06.015