title: Assessment and clinical implications of RANK/RANKL/OPG pathway as markers of bone tumor progression in patients with NET harboring bone metastases.
abstract: BACKGROUND
  The impact on the survival of bone metastases (BM) in patients with neuroendocrine tumor (NET) is a matter of debate. BM have a key role in causing symptoms and in decreasing patients' quality of life. Although the mechanisms of the development of BM are not completely clear, it is now well understood that the Receptor Activator of Nuclear factor Kappa-B-/Ligand (RANK/RANKL)/osteoprotegerin (OPG) pathway plays a relevant role.
  
  
  OBJECTIVE
  To characterize the RANK/RANKL/OPG pathway in patients affected with NET.
  
  
  METHODS
  Two cohorts of 15 patients each were enrolled in the study; one cohort was affected with NET without BM and the second cohort was affected with NET with BM. The serum RANK/RANKL/OPG pathway was assessed in both the groups.
  
  
  RESULTS
  Serum OPG levels and RANKL/OPG ratio were lower and higher, respectively, in NET patients harboring BM than in those without BM. During the ROC analysis, a cut-off value of 1071 pg/ml for OPG and 0.62 for RANKL/OPG ratio were able to significantly distinguish between the two groups.
  
  
  CONCLUSIONS
  This study indicates that RANK/RANKL/OPG pathway is imbalanced in patients with NET harboring BM. Specific alterations of this pathway could predict an early development of BM.
authors: Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy.
authors: F
authors: F
authors: Milone
authors: C
authors: C
authors: Pivonello
authors: F
authors: F
authors: Cariati
authors: M
authors: M
authors: Sarnataro
authors: V
authors: V
authors: Ramundo
authors: V
authors: V
authors: Marotta
authors: H
authors: H
authors: Jann
authors: U-F
authors: UF
authors: Pape
authors: B
authors: B
authors: Wiedenmann
authors: A
authors: A
authors: Colao
authors: M
authors: M
authors: Pavel
authors: A
authors: A
authors: Faggiano
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D018278:Carcinoma, Neuroendocrine / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007414:Intestinal Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D053245:RANK Ligand / Q000097:blood / Q000235:genetics*; D012372:ROC Curve; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000097:blood / Q000235:genetics*; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human