確定PTHrP(12-48)作為一種與乳腺癌骨轉移相關的血漿生物標誌物
Identification of PTHrP(12-48) as a plasma biomarker associated with breast cancer bone metastasis.
Abstract
Breast cancer bone metastasis (BM) is a complication that significantly compromises patient survival due, in part, to the lack of disease-specific biomarkers that allow early and accurate diagnosis Using mass spectrometry protein profiling, plasma samples were screened from 3 independent breast cancer patient cohorts with and without clinical evidence of bone metastasis. 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 BM patients plasma compared with patients without BM (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). These data demonstrate that PTHrP(12-48) circulates in breast cancer patient plasma and is a novel and predictive biomarker of breast cancer BM. Importantly, the clinical measurement of PTHrP(12-48) in combination with NTx improves the detection of breast cancer BM. In summary, we present the first validated, plasma biomarker signature for diagnosis of breast cancer BM that may improve the early diagnosis of high-risk individuals.
