title: Identification of PTHrP(12-48) as a plasma biomarker associated with breast cancer bone metastasis.
abstract: BACKGROUND
  Breast cancer bone metastasis is a complication that significantly compromises patient survival due, in part, to the lack of disease-specific biomarkers that allow early and accurate diagnosis.
  
  
  METHODS
  Using mass spectrometry protein profiling, plasma samples were screened from three independent breast cancer patient cohorts with and without clinical evidence of bone metastasis.
  
  
  RESULTS
  The results identified 13 biomarkers that classified all 110 patients with a sensitivity of 91% and specificity of 93% [receiver operating characteristics area under the curve (AUC = 1.00)]. The most discriminatory protein was subsequently identified as a unique 12-48aa peptide fragment of parathyroid hormone-related protein (PTHrP). PTHrP(12-48) was significantly increased in plasma of patients with bone metastasis compared with patients without bone metastasis (P < 0.0001). Logistic regression models were used to evaluate the diagnostic potential of PTHrP(12-48) as a single biomarker or in combination with the measurement of the clinical marker N-telopeptide of type I collagen (NTx). The PTHrP(12-48) and NTx logistic regression models were not significantly different and classified the patient groups with high accuracy (AUC = 0.85 and 0.95), respectively. Interestingly, in combination with serum NTx, the plasma concentration of PTHrP(12-48) increased diagnostic specificity and accuracy (AUC = 0.99).
  
  
  CONCLUSIONS
  These data show that PTHrP(12-48) circulates in plasma of patient with breast cancer and is a novel and predictive biomarker of breast cancer bone metastasis. Importantly, the clinical measurement of PTHrP(12-48) in combination with NTx improves the detection of breast cancer bone metastasis.
  
  
  CONCLUSIONS
  In summary, we present the first validated, plasma biomarker signature for diagnosis of breast cancer bone metastasis that may improve the early diagnosis of high-risk individuals.
authors: Department of Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors: Charity L
authors: CL
authors: Washam
authors: Stephanie D
authors: SD
authors: Byrum
authors: Kim
authors: K
authors: Leitzel
authors: Suhail M
authors: SM
authors: Ali
authors: Alan J
authors: AJ
authors: Tackett
authors: Dana
authors: D
authors: Gaddy
authors: Suzanne E
authors: SE
authors: Sundermann
authors: Allan
authors: A
authors: Lipton
authors: Larry J
authors: LJ
authors: Suva
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood* / Q000556:secondary*; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments