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Oncotarget. 2018 Jan 3;9(6):7101-7111. doi: 10.18632/oncotarget.23872. eCollection 2018 Jan 23.

Meta-analysis of a 10-plex urine-based biomarker assay for the detection of bladder cancer.

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Department of Urology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Department of Urology, University of Washington, Seattle, WA 98195, USA.
Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL 32224, USA.
Nonagen Bioscience Corporation, Jacksonville, FL 32216, USA.
Department of Biostatistics, The University of Florida, Gainesville, FL 32611, USA.
Clinical & Translational Research Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.


A 10-plex urine-based bladder cancer (BCa) diagnostic signature has the potential to non-invasively predict the presence of BCa in at-risk patients, as reported in various case-control studies. The present meta-analysis was performed to re-evaluate and demonstrate the robustness and consistency of the diagnostic utility of the 10-plex urine-based diagnostic assay. We re-analyzed primary data collected in five previously published case-control studies on the 10-plex diagnostic assay. Studies reported the sensitivity and specificity of ten urinary protein biomarkers for the detection of BCa, including interleukin 8, matrix metalloproteinases 9 and 10, angiogenin, apolipoprotein E, syndecan 1, alpha-1 antitrypsin, plasminogen activator inhibitor-1, carbonic anhydrase 9, and vascular endothelial growth factor A. Data were extracted and reviewed independently by two investigators. Log odds ratios (ORs) were calculated to determine how strongly the 10-plex biomarker panel and individual biomarkers are associated with the presence of BCa. Data pooled from 1,173 patients were analyzed. The log OR for each biomarker was improved by 1.5 or greater with smaller 95% CI in our meta-analysis of the overall cohort compared with each analysis of an individual cohort. The combination of the ten biomarkers showed a higher log OR (log OR: 3.46, 95% CI: 2.60-4.31) than did any single biomarker irrespective of histological grade or disease stage of tumors. We concluded that the 10-plex BCa-associated diagnostic signature demonstrated a higher potential to identify BCa when compared to any single biomarker. Our results justify further advancement of the 10-plex protein-based diagnostic signature toward clinical application.


diagnosis; meta-analysis; urinary bladder; urine biomarkers; urothelial carcinoma

Conflict of interest statement

CONFLICTS OF INTEREST C.J. Rosser and S. Goodison are officers for Nonagen BioScience Corp. Norihiko Masuda, Osamu Ogawa, Meyeon Park, Alvin Y Liu, Yunfeng Dai, Landon Kozai, Hideki Furuya, Yair Lotan, and Takashi Kobayashi declare that they have no conflicts of interest.

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