Detection of glypican-1 (GPC-1) expression in urine cell sediments in prostate cancer

While measurement of serum prostate specific antigen (PSA) is an important screening tool for prostate cancer, new biomarkers are necessary for better discrimination between presence and absence of disease. The MIL-38 monoclonal antibody is specific for the membrane glycoprotein glypican 1 (GPC-1) a...

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Published inPloS one Vol. 13; no. 4; p. e0196017
Main Authors Campbell, Douglas H, Lund, Maria E, Nocon, Aline L, Cozzi, Paul J, Frydenberg, Mark, De Souza, Paul, Schiller, Belinda, Beebe-Dimmer, Jennifer L, Ruterbusch, Julie J, Walsh, Bradley J
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 19.04.2018
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Abstract While measurement of serum prostate specific antigen (PSA) is an important screening tool for prostate cancer, new biomarkers are necessary for better discrimination between presence and absence of disease. The MIL-38 monoclonal antibody is specific for the membrane glycoprotein glypican 1 (GPC-1) and binds to prostate cancer tissue. Urine is known to be a source of cellular material. Thus, we hypothesized that detection of GPC-1 in urine cellular material may identify individuals with prostate cancer. Urine samples from patients with prostate cancer, benign prostatic hyperplasia (BPH), or normal controls were collected and cell sediments prepared. GPC-1-positive cells were detected using a MIL-38 immunofluorescence assay (IFA) and samples were classed positive or negative for GPC-1 expressing cells. Assay sensitivity and specificity, stratified by PSA, was reported. A total of 125 patient samples were analyzed (N = 41 prostate cancer; N = 37 BPH; N = 47 normal controls). The use of MIL-38 to detect GPC-1 by IFA discriminated between prostate cancer and BPH urine specimens with a sensitivity and specificity of 71% and 76%, respectively. Assay specificity increased with increasing PSA, with the highest specificity (89%) for patients with PSA ≥4 ng/ml. At lower PSA (<2 ng/ml) specificity decreased, as evidenced by a greater number of false positives in this concentration range. The odds ratio (OR) and 95% confidence intervals (CIs) for GPC-1-positive cells in patients with prostate cancer, adjusted for PSA, was greatest at the lowest serum PSA (<2 ng/ml; OR = 13.4; 95% CI: 4.0-44.7) compared with no adjustment for PSA (OR = 6.4; 95% CI: 2.8-14.9). The use of MIL-38 for detection of GPC-1 may be a useful tool for detection of prostate cancer.
AbstractList While measurement of serum prostate specific antigen (PSA) is an important screening tool for prostate cancer, new biomarkers are necessary for better discrimination between presence and absence of disease. The MIL-38 monoclonal antibody is specific for the membrane glycoprotein glypican 1 (GPC-1) and binds to prostate cancer tissue. Urine is known to be a source of cellular material. Thus, we hypothesized that detection of GPC-1 in urine cellular material may identify individuals with prostate cancer. Urine samples from patients with prostate cancer, benign prostatic hyperplasia (BPH), or normal controls were collected and cell sediments prepared. GPC-1-positive cells were detected using a MIL-38 immunofluorescence assay (IFA) and samples were classed positive or negative for GPC-1 expressing cells. Assay sensitivity and specificity, stratified by PSA, was reported. A total of 125 patient samples were analyzed (N = 41 prostate cancer; N = 37 BPH; N = 47 normal controls). The use of MIL-38 to detect GPC-1 by IFA discriminated between prostate cancer and BPH urine specimens with a sensitivity and specificity of 71% and 76%, respectively. Assay specificity increased with increasing PSA, with the highest specificity (89%) for patients with PSA ≥4 ng/ml. At lower PSA (<2 ng/ml) specificity decreased, as evidenced by a greater number of false positives in this concentration range. The odds ratio (OR) and 95% confidence intervals (CIs) for GPC-1-positive cells in patients with prostate cancer, adjusted for PSA, was greatest at the lowest serum PSA (<2 ng/ml; OR = 13.4; 95% CI: 4.0-44.7) compared with no adjustment for PSA (OR = 6.4; 95% CI: 2.8-14.9). The use of MIL-38 for detection of GPC-1 may be a useful tool for detection of prostate cancer.
While measurement of serum prostate specific antigen (PSA) is an important screening tool for prostate cancer, new biomarkers are necessary for better discrimination between presence and absence of disease. The MIL-38 monoclonal antibody is specific for the membrane glycoprotein glypican 1 (GPC-1) and binds to prostate cancer tissue. Urine is known to be a source of cellular material. Thus, we hypothesized that detection of GPC-1 in urine cellular material may identify individuals with prostate cancer. Urine samples from patients with prostate cancer, benign prostatic hyperplasia (BPH), or normal controls were collected and cell sediments prepared. GPC-1-positive cells were detected using a MIL-38 immunofluorescence assay (IFA) and samples were classed positive or negative for GPC-1 expressing cells. Assay sensitivity and specificity, stratified by PSA, was reported. A total of 125 patient samples were analyzed (N = 41 prostate cancer; N = 37 BPH; N = 47 normal controls). The use of MIL-38 to detect GPC-1 by IFA discriminated between prostate cancer and BPH urine specimens with a sensitivity and specificity of 71% and 76%, respectively. Assay specificity increased with increasing PSA, with the highest specificity (89%) for patients with PSA [greater than or equal to]4 ng/ml. At lower PSA (<2 ng/ml) specificity decreased, as evidenced by a greater number of false positives in this concentration range. The odds ratio (OR) and 95% confidence intervals (CIs) for GPC-1-positive cells in patients with prostate cancer, adjusted for PSA, was greatest at the lowest serum PSA (<2 ng/ml; OR = 13.4; 95% CI: 4.0-44.7) compared with no adjustment for PSA (OR = 6.4; 95% CI: 2.8-14.9). The use of MIL-38 for detection of GPC-1 may be a useful tool for detection of prostate cancer.
Audience Academic
Author Campbell, Douglas H
De Souza, Paul
Schiller, Belinda
Lund, Maria E
Beebe-Dimmer, Jennifer L
Ruterbusch, Julie J
Walsh, Bradley J
Nocon, Aline L
Frydenberg, Mark
Cozzi, Paul J
AuthorAffiliation Duke University School of Medicine, UNITED STATES
6 Department of Medical Oncology, Liverpool Hospital, Sydney, New South Wales, Australia
7 School of Medicine, University of Western Sydney, Sydney, New South Wales, Australia
1 Minomic International Ltd, Sydney, New South Wales, Australia
9 Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, United States of America
2 St George and Sutherland Clinical School, the University of New South Wales, Sydney, New South Wales, Australia
4 Epworth Healthcare, Melbourne, Victoria, Australia
8 Karmanos Cancer Institute, Detroit, Michigan, United States of America
3 Department of Surgery, St George Hospital, Sydney, New South Wales, Australia
5 Department of Surgery, Monash University, Melbourne, Victoria, Australia
AuthorAffiliation_xml – name: 8 Karmanos Cancer Institute, Detroit, Michigan, United States of America
– name: Duke University School of Medicine, UNITED STATES
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/29672570$$D View this record in MEDLINE/PubMed
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2018 Campbell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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– notice: 2018 Campbell et al 2018 Campbell et al
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Competing Interests: PDS received research funding from Atridia Pty Ltd and Suzhou NeuPharma Co, Ltd. BS is an employee of Astellas Australia Pty Ltd. JBD and JR received consulting fees from CUSP LLC. DHC is Head of Research and Development at Minomic International Ltd and owns shares in Minomic International Ltd. BJW is CEO of Minomic International Ltd and owns shares in Minomic International Ltd. ML and AN are employees of Minomic International Ltd and both own shares in Minomic International Ltd. PC and MF have no conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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Snippet While measurement of serum prostate specific antigen (PSA) is an important screening tool for prostate cancer, new biomarkers are necessary for better...
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SubjectTerms Antigens
Assaying
Biological products
Biology and Life Sciences
Biomarkers
Biopsy
Bladder
Cancer
Cancer screening
Care and treatment
Cellular biology
Confidence intervals
Diagnosis
Earth Sciences
Glycoproteins
Health aspects
Heparan sulfate
Heparan sulfate proteoglycans
Hyperplasia
Immunofluorescence
Medical diagnosis
Medical research
Medicine
Medicine and Health Sciences
Monoclonal antibodies
Oncology
Patients
Prostate cancer
Prostatic hyperplasia
Research and Analysis Methods
Sediments
Sensitivity
Surveillance
Urine
Urology
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Title Detection of glypican-1 (GPC-1) expression in urine cell sediments in prostate cancer
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http://dx.doi.org/10.1371/journal.pone.0196017
Volume 13
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