Pii-Lba3 Glypican-1 as a Biomarker for Prostate Cancer

Shore, Neal D.; Concepcion, Raoul; Saltzstein, Daniel R.; Paivanas, Thomas A.; Beebe‐Dimmer, Jennifer L.; Ruterbusch, Julie J.; Justiniano, Irene; Mazure, Hubert; Nocon, Aline L.; Soon, Julie; Truong, Quach; Wissmueller, Sandra; Campbell, Douglas Houghton; Walsh, Bradley J.

doi:10.1016/j.juro.2015.03.083

Cited by 4 publications

(2 citation statements)

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“…Future studies are underway to develop a MIL-38 based GPC-1 ELISA to assess the levels of GPC-1 in normal, BPH and prostate cancer patients to determine whether secreted GPC-1 may represent a clinically relevant biomarker for prostate cancer diagnosis. Preliminary data presented at the 2015 American Urology Association supports GPC-1 as an unrelated candidate biomarker with improved specificity (79%) over PSA 35 , thereby reducing false positive reporting and the need for unnecessary biopsies. Furthermore, MIL-38 labelled with alpha emitting radioactive isotopes is able to suppress the growth of human prostate cancer subcutaneous xenografts in vivo 36 and also as a targeting antibody for tissue specific gene therapy delivery 37 .…”

Section: Discussionmentioning

confidence: 98%

Glypican-1 as a Biomarker for Prostate Cancer: Isolation and Characterization

Truong¹,

Justiniano²,

Nocon³

et al. 2016

J. Cancer

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Prostate cancer is the most frequently diagnosed male visceral cancer and the second leading cause of cancer death in the United States. Standard tests such as prostate-specific antigen (PSA) measurement have poor specificity (33%) resulting in a high number of false positive reports. Consequently there is a need for new biomarkers to address this problem. The MIL-38 antibody was first described nearly thirty years ago, however, until now, the identification of the target antigen remained elusive. By a series of molecular techniques and mass spectrometry, the MIL-38 antigen was identified to be the highly glycosylated proteoglycan Glypican-1 (GPC-1). This protein is present in two forms; a membrane bound core protein of 55-60 kDa and secreted soluble forms of 40 kDa and 52 kDa. GPC-1 identification was confirmed by immuno-precipitation, western blots and ELISA. An ELISA platform is currently being developed to assess the levels of GPC-1 in normal, benign prostatic hyperplasia (BPH) and prostate cancer patients to determine whether secreted GPC-1 may represent a clinically relevant biomarker for prostate cancer diagnosis.

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Section: Discussionmentioning

confidence: 98%

Glypican-1 as a Biomarker for Prostate Cancer: Isolation and Characterization

Truong¹,

Justiniano²,

Nocon³

et al. 2016

J. Cancer

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“…These assays are commonly limited by the autofluorescence background and the spectral crosstalk between the multiple fluorescent colors, as well as the photo-bleaching issue of the fluorophores. Quantitative detection of the low abundant biomolecule analytes and monitoring their changes in the blood [6], particularly along the development and treatment of cancer [7,8], require new luminescent probes and detection schemes to achieve the high sensitivity and throughput [6,9]. Upconversion nanoparticles (UCNPs) emit visible light by NIR excitation [10].…”

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confidence: 99%

Upconversion nanoparticle‐assisted single‐molecule assay for detecting circulating antigens of aggressive prostate cancer

et al. 2021

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Sensitive and quantitative detection of molecular biomarkers is crucial for the early diagnosis of diseases like metabolic syndrome and cancer. Here we present a single‐molecule sandwich immunoassay by imaging the number of single nanoparticles to diagnose aggressive prostate cancer. Our assay employed the photo‐stable upconversion nanoparticles (UCNPs) as labels to detect the four types of circulating antigens in blood circulation, including glypican‐1 (GPC‐1), leptin, osteopontin (OPN), and vascular endothelial growth factor (VEGF), as their serum concentrations indicate aggressive prostate cancer. Under a wide‐field microscope, a single UCNP doped with thousands of lanthanide ions can emit sufficiently bright anti‐Stokes' luminescence to become quantitatively detectable. By counting every single streptavidin‐functionalized UCNP which specifically labeled on each sandwich immune complex across multiple fields of views, we achieved the Limit of Detection (LOD) of 0.0123 ng/ml, 0.2711 ng/ml, 0.1238 ng/ml, and 0.0158 ng/ml for GPC‐1, leptin, OPN and VEGF, respectively. The serum circulating level of GPC‐1, leptin, OPN, and VEGF in a mixture of 10 healthy normal human serum was 25.17 ng/ml, 18.04 ng/ml, 11.34 ng/ml, and 1.55 ng/ml, which was within the assay dynamic detection range for each analyte. Moreover, a 20% increase of GPC‐1 and OPN was observed by spiking the normal human serum with recombinant antigens to confirm the accuracy of the assay. We observed no cross‐reactivity among the four biomarker analytes, which eliminates the false positives and enhances the detection accuracy. The developed single upconversion nanoparticle‐assisted single‐molecule assay suggests its potential in clinical usage for prostate cancer detection by monitoring tiny concentration differences in a panel of serum biomarkers.

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