Hypercalcemia Due to PTHrP

Kremer, Richard; Goltzman, David

doi:10.1016/b978-012098651-4/50044-4

Cited by 1 publication

(1 citation statement)

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“…Human PTHrP exists in three different isoforms of 139, 141, and 173 amino acids. All isoforms have identical sequences for residues 1-139. ,, These isoforms undergo post-translational cleavage to generate fragments including PTHrP 1-86, PTHrP 1-33, PTHrP 151-169, PTHrP 140-173, each with distinct biological roles. , Current commercial tests for PTHrP fragments can only detect them in serum or blood after the development of hypercalcemia (PTHrP > 10 pg mL –1 ) when there is a 50% chance of mortality in 30 days and a slight prospect for therapeutic intervention. ,− In addition, methods such as immunoradiometric (IRMA) and radioimmunoassay (RIA) pose health hazards due to the usage of short shelf-life high-energy isotopes, such as 125 I. , Moreover, these assays have no multiplexing capability and cannot tease out specific isoforms, in particular the unique human-specific PTHrP 1-173. Furthermore, limits of detection (LOD) 3 pg mL –1 for IRMA, , 40 pg mL –1 for RIA, , 6 pg mL –1 for mass spectroscopy, 5 pg mL –1 for immunofluorometric assays (IFMA), and 5 pg mL –1 for ELISA are insufficient to establish the normal range from healthy volunteers and cannot detect PTHrP in normocalcemic cancer patients.…”

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confidence: 99%

Immunoarray Measurements of Parathyroid Hormone-Related Peptides Combined with Other Biomarkers to Diagnose Aggressive Prostate Cancer

et al. 2022

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Parathyroid hormone-related peptide (PTHrP) is related to bone metastasis and hypercalcemia in prostate and breast cancers and should be an excellent biomarker for aggressive forms of these cancers. Current clinical detection protocols for PTHrP are immunoradiometric assay and radioimmunoassay but are not sensitive enough to detect PTHrPs at early stages. We recently evaluated a prostate cancer biomarker panel, including serum monocyte differentiation antigen (CD-14), ETS-related gene protein, pigment epithelial-derived factor, and insulin-like growth factor-1, with promise for identifying aggressive prostate cancers. This panel predicted the need for patient biopsy better than PSA alone. In the present paper, we report an ultrasensitive microfluidic assay for PTHrPs and evaluate their diagnostic value and the value of including them with our prior biomarker panel to diagnose aggressive forms of prostate cancer. The immunoarray features screen-printed carbon sensor electrodes coated with 5 nm glutathione gold nanoparticles with capture antibodies attached. PTHrPs are bound to a secondary antibody attached to a polyhorseradish peroxidase label and delivered to the sensors to provide high sensitivity when activated by H2O2 and a mediator. We obtained an unprecedented 0.3 fg mL–1 limit of detection for PTHrP bioactive moieties PTHrP 1-173 and PTHrP 1-86. We also report the first study of PTHrPs in a large serum pool to identify aggressive malignancies. In assays of 130 human patient serum samples, PTHrP levels distinguished between aggressive and indolent prostate cancers with 83–91% clinical sensitivity and 78–96% specificity. Logistic regression identified the best predictive model as a combination of PTHrP 1-86 and vascular endothelial growth factor-D. PTHrP 1-173 alone also showed a high ability to differentiate aggressive and indolent cancers.

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