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Cited by 109Bladder and Urothelial Cancer TreatmentsUrinary Bladder and Prostate ResearchUrinary Tract Infections Management

A multi-analyte assay for the non-invasive detection of bladder cancer

Open access
Goodison, Steve, Chang, Myron, Dai, Yunfeng, Urquidi, Virginia, Rosser, Charles J.·2012·PLoS ONE
DOI 10.1371/journal.pone.0047469PMC PMC3477150
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Abstract

Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.

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  • Mechanisms underlying the association between high apoE levels and increased cancer mortality could likely be due to apoE involvement in metastasis and angiogenesis.

    “mechanisms underlying the association between high apoE levels and increased cancer mortality could likely be due to apoE involvement in metastasis and angiogenesis.49–56”

    From Plasma levels of apolipoprotein E, <i>APOE</i> genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort (2019) · cites this paper as [49]

    The Discussion (page not specified) describes APOE in bladder tumor cells in terms of cell turnover and resistance to apoptosis, but does not link high APOE levels to cancer mortality, metastasis, or angiogenesis. A separate Discussion passage attributes angiogenic properties and metastasis in mouse models to IL-8, not APOE. Searches for APOE with mortality, metastasis, and angiogenesis found no passage supporting the claimed mechanism. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Goodison, S., Chang, M., Dai, Y., Urquidi, V., & Rosser, C. J.
Affiliations
  • University of Florida (US)
  • Nonagen Bioscience (United States) (US)
Corresponding author
Rosser, Charles J.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-10-19
Volume
7
Issue
10
Pages
e47469
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0047469
PMC
PMC3477150
OpenAlex
W2068140176
Cited by
109
References
1
Citations by year
2026: 3 · 2025: 8 · 2024: 7 · 2023: 2 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 14 · 2015: 8 · 2014: 13 · 2013: 9
FWCI
9.34
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Flight Attendant Medical Research Institute
  • Florida Department of Health
  • National Institutes of Health (UL1TR000064)
  • National Cancer Institute (R01CA116161)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
  • Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
  • Health Sciences › Medicine › Epidemiology › Urinary Tract Infections Management
Keywords
bladder cancer, non-invasive cancer detection, urinary biomarkers, interleukin-8, vascular endothelial growth factor, apolipoprotein E, urine cytology, diagnostic accuracy, proteomic profiling
MeSH terms
Adult, Aged, Aged, 80 and over, Apolipoproteins E, Urinary Bladder, Urinary Bladder Neoplasms, Carcinoma, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Neoplasm Staging, ROC Curve, Biomarkers, Tumor, Multivariate Analysis, Case-Control Studies, Interleukin-8, Vascular Endothelial Growth Factor A, Neoplasm Grading

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