Plasma levels of receptor activator of nuclear factor‐κB ligand and osteoprotegerin in patients with neuroblastoma

Abstract

Earlier reports showed that the balance between receptor activator of nuclear factor-jB ligand (RANKL) and its decoy-receptor osteoprotegerin (OPG) plays an important role in the pathogenesis of metastatic osteolysis induced by neuroblastoma cells. In this study, we investigated whether circulating levels of OPG, RANKL and their ratio were associated to the presence of osteolytic lesions in advanced neuroblastoma, as well as whether they provided additional information on the severity and prognosis of the disease. Plasma levels of RANKL and OPG were measured in 54 newly diagnosed neuroblastomas; 27 of them showed metastatic disease (stage IV), including 19 bone dissemination. Thirty-five children who were admitted to the pediatric department for minor surgical problems served as control group. OPG was significantly lower in all patients compared with controls, while RANKL levels were significantly increased in advanced neuroblastoma. OPG-to-RANKL ratio decreased in stage-IV patients, and particularly in those who had bone metastases. The diagnostic accuracy of the OPG-to-RANKL ratio in discriminating the presence of osteolytic lesions was not confirmed statistically. OPG correlated significantly with other prognostic factors, namely, ferritin and neurone-specific enolase. In addition, an inverse relationship was found between OPG and event-free survival, and it was more significant in patients who had bone metastasis. This pilot study confirms that the production of OPG and RANKL is disregulated in neuroblastoma. Although the OPG-to-RANKL ratio does not have a predictive value in detecting bone metastasis, the measurement of the previously mentioned markers could be useful in decisions regarding the use of adjuvant therapies. ' 2006 Wiley-Liss, Inc.

Prognostic Significance of Interleukin-6 Single Nucleotide Polymorphism Genotypes in Neuroblastoma:rs1800795(Promoter) andrs8192284(Receptor)

“…Individuals who harbor the homozygous G/G polymorphism produce IL-6 concentrations of [5.35 ± 3.01 pg/L] compared with those carrying G/C [3.96 ± 2.71 pg/ml] or C/C [3.52 ± 2.4 pg/ml] (G/G versus C/C, P-value < 0.05) 29 and other studies support a similar association between the G allele and elevated serum IL-6 levels in healthy volunteers 23, 24. Data from several studies have demonstrated that the -174 IL-6 (G>C) SNP results in a functional alteration which affects gene transcription and subsequent serum levels of IL-6 cytokine 23, 24, 26–28, 32–35. These data support the use of the -174 IL-6 (G>C) SNP genotype as a surrogate marker of cumulative IL-6 exposure.…”

A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients

“…There is a keen interest in biomarkers contained in body fluids because they are easy obtainable and can give indications about the response to therapy. These biomarkers includes catecholamines, ferritin, LDH [62], and other factors such as midkine [63], RANKL and OPG [64] but they do not define all risk groups and they can not substitute the analysis of the tumor mass. For the time being, the combination of tumor and body fluid characterization is needed for the optimal assessment of the treatment.…”

RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases

“…This hypothesis is strengthened by the effect of bisphosphonate treatment which results in a decrease in the OPG level in contrast to RANKL which is not modified [109,110]. In fine, as the RANKL/ OPG ratio is significantly higher in patients with severe malignant osteolytic pathologies [106,[111][112][113], it could predict survival as demonstrated in multiple myeloma [114]. Moreover, the RANKL/ OPG ratio may be used as a prognostic biological marker in non-malignant pathologies such as osteoporosis [108,115], ankylosing spondylitis [116], rheumatoid arthritis [117], benign bone tumors, osteolysis associated with hip prosthetic loosening [106,118,119] or bone fractures [120].…”