TY - JOUR
T1 - A multiplex urinary immunoassay for bladder cancer detection
T2 - Analysis of a Japanese cohort
AU - Goodison, Steve
AU - Ogawa, Osamu
AU - Matsui, Yoshiyuki
AU - Kobayashi, Takashi
AU - Miyake, Makito
AU - Ohnishi, Sayuri
AU - Fujimoto, Kiyohide
AU - Dai, Yunfeng
AU - Shimizu, Yoshiko
AU - Tsukikawa, Kazue
AU - Furuya, Hideki
AU - Rosser, Charles J.
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016/10/7
Y1 - 2016/10/7
N2 - Background: Bladder cancer (BCa) is among the most commonly diagnosed malignancies worldwide, and due the high rate of post-operative disease recurrence, it is one of the most prevalent in many countries. The development of non-invasive molecular assays that can accurately detect and monitor BCa would be a major advance, benefiting both patients and healthcare systems. We have previously identified a urinary protein biomarker panel that is being developed for application in at-risk patient cohorts. Here, we investigated the potential utility of the multiplex assay in a Japanese cohort. Methods: The Japanese study cohort collected from urology clinics at two institutions was comprised of a total of 288 subjects. The protein biomarker panel (IL8, MMP9, MMP10, ANG, APOE, SDC1, A1AT, PAI1, CA9, VEGFA) was monitored in voided urine samples collected prior to cystoscopy using a custom multiplex ELISA assay. The diagnostic performance of the biomarker panel was assessed using receiver operator curves, predictive modeling and descriptive statistics. Results: Urinary biomarker concentrations were significantly elevated in cases versus controls, and in cases with high-grade and muscle-invasive tumors. The AUC for the 10-biomarker assay was 0.892 (95 % confidence interval 0.850-0.934), with an overall diagnostic sensitivity specificity of 0.85 and 0.81, respectively. A predictive model trained on the larger institutional cohort correctly identified 99 % of the cases from the second institution. Conclusions: Urinary levels of a 10-biomarker panel enabled discrimination of patients with BCa. The multiplex urinary diagnostic assay has the potential to be developed for the non-invasive detection of BCa in at-risk Japanese patients.
AB - Background: Bladder cancer (BCa) is among the most commonly diagnosed malignancies worldwide, and due the high rate of post-operative disease recurrence, it is one of the most prevalent in many countries. The development of non-invasive molecular assays that can accurately detect and monitor BCa would be a major advance, benefiting both patients and healthcare systems. We have previously identified a urinary protein biomarker panel that is being developed for application in at-risk patient cohorts. Here, we investigated the potential utility of the multiplex assay in a Japanese cohort. Methods: The Japanese study cohort collected from urology clinics at two institutions was comprised of a total of 288 subjects. The protein biomarker panel (IL8, MMP9, MMP10, ANG, APOE, SDC1, A1AT, PAI1, CA9, VEGFA) was monitored in voided urine samples collected prior to cystoscopy using a custom multiplex ELISA assay. The diagnostic performance of the biomarker panel was assessed using receiver operator curves, predictive modeling and descriptive statistics. Results: Urinary biomarker concentrations were significantly elevated in cases versus controls, and in cases with high-grade and muscle-invasive tumors. The AUC for the 10-biomarker assay was 0.892 (95 % confidence interval 0.850-0.934), with an overall diagnostic sensitivity specificity of 0.85 and 0.81, respectively. A predictive model trained on the larger institutional cohort correctly identified 99 % of the cases from the second institution. Conclusions: Urinary levels of a 10-biomarker panel enabled discrimination of patients with BCa. The multiplex urinary diagnostic assay has the potential to be developed for the non-invasive detection of BCa in at-risk Japanese patients.
KW - Biomarkers
KW - Bladder cancer
KW - Multiplex
KW - Protein
KW - Urine
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U2 - 10.1186/s12967-016-1043-1
DO - 10.1186/s12967-016-1043-1
M3 - Article
C2 - 27717367
AN - SCOPUS:84990855470
SN - 1479-5876
VL - 14
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
IS - 1
M1 - 287
ER -