Abstract
Bone metastases are a frequent event in patients with solid tumors. Although great advances have been made in the treatment of these patients, the identification of novel, accurate indicators of bone response would greatly facilitate the clinical management of the disease. The receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway is significantly involved in bone metastasis formation. The main aim of the present study was to evaluate the role of circulating RANK, RANKL and OPG levels in predicting bone response. Marker accuracy was also compared with that of the conventional tumor marker N-terminal telopeptide of type I collagen (NTX). A prospective study was performed on 49 patients with bone metastases from breast, lung and prostate cancer, who were undergoing treatment with zoledronic acid. Patients were monitored for 1 year with blood tests, clinical evaluation and instrumental exams according to the response evaluation criteria of the University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the Positron Emission Tomography Response Criteria in Solid Tumors. Circulating RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription-quantitative polymerase chain reaction and immune enzymatic assay, respectively. The baseline RANKL levels differed significantly between responders and non-responders, whereas no differences in NTX levels were observed between the two groups. Receiver operating characteristic curve evaluation for all markers revealed that RANKL was the most accurate marker, with an area under the curve of 0.74 (95% confidence interval, 0.54-0.93). In addition, RANKL, which is the target of the novel monoclonal antibody denosumab, was the most accurate predictor of bone response in the present series of patients with bone metastases. Thus, the use of RANKL as a marker could potentially improve clinical practice, as current bone response evaluation is still somewhat problematic.
| Original language | English |
|---|---|
| Pages (from-to) | 2970-2975 |
| Number of pages | 6 |
| Journal | Oncology Letters |
| Volume | 12 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Oct 1 2016 |
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Keywords
- Bone metastases
- NTX
- OPG
- RANK
- RANKL
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
RANKL : A promising circulating marker for bone metastasis response. / Ibrahim, Toni; Ricci, Marianna; Scarpi, Emanuela; Bongiovanni, Alberto; Ricci, Rossana; Riva, Nada; Liverani, Chiara; De Vita, Alessandro; La Manna, Federico; Oboldi, Devil; Serra, Patrizia; Foca, Flavia; Cecconetto, Lorenzo; Amadori, Dino; Mercatali, Laura.
In: Oncology Letters, Vol. 12, No. 4, 01.10.2016, p. 2970-2975.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - RANKL
T2 - A promising circulating marker for bone metastasis response
AU - Ibrahim, Toni
AU - Ricci, Marianna
AU - Scarpi, Emanuela
AU - Bongiovanni, Alberto
AU - Ricci, Rossana
AU - Riva, Nada
AU - Liverani, Chiara
AU - De Vita, Alessandro
AU - La Manna, Federico
AU - Oboldi, Devil
AU - Serra, Patrizia
AU - Foca, Flavia
AU - Cecconetto, Lorenzo
AU - Amadori, Dino
AU - Mercatali, Laura
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Bone metastases are a frequent event in patients with solid tumors. Although great advances have been made in the treatment of these patients, the identification of novel, accurate indicators of bone response would greatly facilitate the clinical management of the disease. The receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway is significantly involved in bone metastasis formation. The main aim of the present study was to evaluate the role of circulating RANK, RANKL and OPG levels in predicting bone response. Marker accuracy was also compared with that of the conventional tumor marker N-terminal telopeptide of type I collagen (NTX). A prospective study was performed on 49 patients with bone metastases from breast, lung and prostate cancer, who were undergoing treatment with zoledronic acid. Patients were monitored for 1 year with blood tests, clinical evaluation and instrumental exams according to the response evaluation criteria of the University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the Positron Emission Tomography Response Criteria in Solid Tumors. Circulating RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription-quantitative polymerase chain reaction and immune enzymatic assay, respectively. The baseline RANKL levels differed significantly between responders and non-responders, whereas no differences in NTX levels were observed between the two groups. Receiver operating characteristic curve evaluation for all markers revealed that RANKL was the most accurate marker, with an area under the curve of 0.74 (95% confidence interval, 0.54-0.93). In addition, RANKL, which is the target of the novel monoclonal antibody denosumab, was the most accurate predictor of bone response in the present series of patients with bone metastases. Thus, the use of RANKL as a marker could potentially improve clinical practice, as current bone response evaluation is still somewhat problematic.
AB - Bone metastases are a frequent event in patients with solid tumors. Although great advances have been made in the treatment of these patients, the identification of novel, accurate indicators of bone response would greatly facilitate the clinical management of the disease. The receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway is significantly involved in bone metastasis formation. The main aim of the present study was to evaluate the role of circulating RANK, RANKL and OPG levels in predicting bone response. Marker accuracy was also compared with that of the conventional tumor marker N-terminal telopeptide of type I collagen (NTX). A prospective study was performed on 49 patients with bone metastases from breast, lung and prostate cancer, who were undergoing treatment with zoledronic acid. Patients were monitored for 1 year with blood tests, clinical evaluation and instrumental exams according to the response evaluation criteria of the University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the Positron Emission Tomography Response Criteria in Solid Tumors. Circulating RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription-quantitative polymerase chain reaction and immune enzymatic assay, respectively. The baseline RANKL levels differed significantly between responders and non-responders, whereas no differences in NTX levels were observed between the two groups. Receiver operating characteristic curve evaluation for all markers revealed that RANKL was the most accurate marker, with an area under the curve of 0.74 (95% confidence interval, 0.54-0.93). In addition, RANKL, which is the target of the novel monoclonal antibody denosumab, was the most accurate predictor of bone response in the present series of patients with bone metastases. Thus, the use of RANKL as a marker could potentially improve clinical practice, as current bone response evaluation is still somewhat problematic.
KW - Bone metastases
KW - NTX
KW - OPG
KW - RANK
KW - RANKL
UR - http://www.scopus.com/inward/record.url?scp=84983398728&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983398728&partnerID=8YFLogxK
U2 - 10.3892/ol.2016.4977
DO - 10.3892/ol.2016.4977
M3 - Article
AN - SCOPUS:84983398728
VL - 12
SP - 2970
EP - 2975
JO - Oncology Letters
JF - Oncology Letters
SN - 1792-1074
IS - 4
ER -