Identification of PTHrP(12-48) as a plasma biomarker associated with breast cancer bone metastasis

Charity L. Washam, Stephanie D. Byrum, Kim Leitzel, Suhail M. Ali, Alan J. Tackett, Dana Gaddy, Suzanne E. Sundermann, Allan Lipton, Larry J. Suva

Research output: Contribution to journalArticle

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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 hormonerelated 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. Impact: 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. Cancer Epidemiol Biomarkers Prev; 22(5); 972-83.

Original languageEnglish (US)
Pages (from-to)972-983
Number of pages12
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number5
DOIs
StatePublished - May 1 2013

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Bone Neoplasms
Biomarkers
Breast Neoplasms
Neoplasm Metastasis
Area Under Curve
Proteins
Logistic Models
Bone and Bones
Early Diagnosis
Peptide Fragments
Tumor Biomarkers
Collagen Type I
ROC Curve
Blood Proteins
Mass Spectrometry
Sensitivity and Specificity
Survival

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

Cite this

Washam, Charity L. ; Byrum, Stephanie D. ; Leitzel, Kim ; Ali, Suhail M. ; Tackett, Alan J. ; Gaddy, Dana ; Sundermann, Suzanne E. ; Lipton, Allan ; Suva, Larry J. / Identification of PTHrP(12-48) as a plasma biomarker associated with breast cancer bone metastasis. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 5. pp. 972-983.
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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 hormonerelated 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. Impact: 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. Cancer Epidemiol Biomarkers Prev; 22(5); 972-83.",
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Washam, CL, Byrum, SD, Leitzel, K, Ali, SM, Tackett, AJ, Gaddy, D, Sundermann, SE, Lipton, A & Suva, LJ 2013, 'Identification of PTHrP(12-48) as a plasma biomarker associated with breast cancer bone metastasis', Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 5, pp. 972-983. https://doi.org/10.1158/1055-9965.EPI-12-1318-T

Identification of PTHrP(12-48) as a plasma biomarker associated with breast cancer bone metastasis. / Washam, Charity L.; Byrum, Stephanie D.; Leitzel, Kim; Ali, Suhail M.; Tackett, Alan J.; Gaddy, Dana; Sundermann, Suzanne E.; Lipton, Allan; Suva, Larry J.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 5, 01.05.2013, p. 972-983.

Research output: Contribution to journalArticle

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T1 - Identification of PTHrP(12-48) as a plasma biomarker associated with breast cancer bone metastasis

AU - Washam, Charity L.

AU - Byrum, Stephanie D.

AU - Leitzel, Kim

AU - Ali, Suhail M.

AU - Tackett, Alan J.

AU - Gaddy, Dana

AU - Sundermann, Suzanne E.

AU - Lipton, Allan

AU - Suva, Larry J.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - 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 hormonerelated 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. Impact: 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. Cancer Epidemiol Biomarkers Prev; 22(5); 972-83.

AB - 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 hormonerelated 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. Impact: 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. Cancer Epidemiol Biomarkers Prev; 22(5); 972-83.

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