Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2014

Open Access 01-12-2014 | Research

Validation and clinicopathologic associations of a urine-based bladder cancer biomarker signature

Authors: Ge Zhang, Evan Gomes-Giacoia, Yunfeng Dai, Adrienne Lawton, Makito Miyake, Hideki Furuya, Steve Goodison, Charles J Rosser

Published in: Diagnostic Pathology | Issue 1/2014

Login to get access

Abstract

Background

To validate the expression of a urine-based bladder cancer associated diagnostic signature comprised of 10 targets; ANG, CA9, MMP9, MMP10, SERPINA1, APOE, SDC1, VEGFA, SERPINE1 and IL8 in bladder tumor tissues.

Methods

Immunohistochemical analyses were performed on tumor specimens from 213 bladder cancer patients (transitional cell carcinoma only) and 74 controls. Staining patterns were digitally captured and quantitated (Aperio, Vista, CA), and expression was correlated with tumor stage, tumor grade and outcome measures.

Results

We revealed a positive association of 9 of the 10 proteins (excluding VEGF) in bladder cancer. Relative to control cases, a reduction in SDC1 and overexpression of MMP9, MMP10, SERPINE1, IL8, APOE, SERPINA1, ANG were associated with high stage bladder cancer. Reduced VEGF and increased SERPINA1 were associated with high-grade bladder cancer. Disease-specific survival was significantly reduced in tumors with high expression of SERPINE1 and/or IL8.

Conclusions

These findings confirm that the proteins in a urine-based diagnostic signature are aberrantly expressed in bladder tumor tissues, and support the potential additional utility of selected biomarkers for the clinicopathological evaluation of excised tissue or biopsy material.

Virtual Slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​13000_​2014_​200
Appendix
Available only for authorised users
Literature
1.
Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 2012, 62 (1): 10-29. 10.3322/caac.20138.PubMedCrossRef
2.
Aben KK, Kiemeney LA: Epidemiology of bladder cancer. Eur Urol. 1999, 36: 660-672. 10.1159/000020069.PubMedCrossRef
3.
Hall MC, Chang SS, Dalbagni G, Pruthi RS, Seigne JD, Skinner EC, Wolf JS, Schellhammer PF: Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. J Urol. 2007, 178 (6): 2314-2330. 10.1016/j.juro.2007.09.003.PubMedCrossRef
4.
Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Böhle A, Palou-Redorta J: EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol. 2008, 54 (2): 303-314. 10.1016/j.eururo.2008.04.051.PubMedCrossRef
5.
6.
Stenzl A, Cowan NC, De Santis M, Kuczyk MA, Merseburger AS, Ribal MJ, Sherif A, Witjes JA: Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines. Eur Urol. 2011, 59 (6): 1009-1018. 10.1016/j.eururo.2011.03.023. doi:10.1016/j.eururo.2011.03.023. Epub 2011 Mar 23. ReviewPubMedCrossRef
7.
Sternberg CN, Donat SM, Bellmunt J, Millikan RE, Stadler W, De Mulder P, Sherif A, von der Maase H, Tsukamoto T, Soloway MS: Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. Urology. 2007, 69 (1 Suppl): 62-79. 10.1016/j.urology.2006.10.041. ReviewPubMedCrossRef
8.
Urquidi V, Goodison S, Rosser CJ: Diagnostic potential of urinary <alpha> 1-antitrypsin and apolipoprotein e in the detection of bladder cancer. J Urol. 2013, S0022-5347 (13): 00051-00057.
9.
Urquidi V, Kim J, Chang M, Dai Y, Rosser CJ, Goodison S: CCL18 in a multiplex urine-based assay for the detection of bladder cancer. PLoS One. 2012, 7 (5): e37797-10.1371/journal.pone.0037797. Epub 2012 May 21PubMedPubMedCentralCrossRef
10.
Urquidi V, Chang M, Dai Y, Kim J, Wolfson ED, Goodison S, Rosser CJ: IL-8 as a urinary biomarker for the detection of bladder cancer. BMC Urol. 2012, 12 (1): 12-10.1186/1471-2490-12-12.PubMedPubMedCentralCrossRef
11.
Urquidi V, Goodison S, Kim J, Chang M, Dai Y, Rosser CJ: Vascular endothelial growth factor, carbonic anhydrase 9, and angiogenin as urinary biomarkers for bladder cancer detection. Urology. 2012, 79 (5): 1185.e1-6-10.1016/j.urology.2012.01.016. Epub 2012 Mar 3PubMedCrossRef
12.
Goodison S, Chang M, Dai Y, Urquidi V, Rosser CJ: A multi-analyte assay for the non-invasive detection of bladder cancer. PLoS One. 2012, 7 (10): e47469-10.1371/journal.pone.0047469.PubMedPubMedCentralCrossRef
13.
Rosser CJ, Ross S, Chang M, Dai Y, Mengual L, Zhang G, Kim J, Urquidi V, Alcaraz A, Goodison S: Multiplex protein signature for the detection of bladder cancer in voided urine samples. J Urol. 2013, 190 (6): 2257-2262. 10.1016/j.juro.2013.06.011. doi:10.1016/j.juro.2013.06.011PubMedPubMedCentralCrossRef
14.
Chen LM, Chang M, Dai Y, Chai KX, Dyrskot L, Sanchez-Carbayo M, Szarvas T, Zwarthoff EC, Lokeshwar V, Jeronimo C, Parker AS, Ross S, Borre M, Orntoft TF, Jaeger T, Beukers W, Lopez LE, Henrique R, Young PR, Urquidi V, Goodison S, Rosser CJ: External validation of a multiplex urinary protein panel for the detection of bladder cancer in a multicenter cohort. Cancer Epidemiol Biomarkers Prev. 2014, 23 (9): 1804-1812. 10.1158/1055-9965.EPI-14-0029.PubMedPubMedCentralCrossRef
15.
Rosser CJ, Chang M, Dai Y, Ross S, Mengual L, Alacaraz A, Goodison S: Urinary protein biomarker panel for the detection of recurrent bladder cancer. Cancer Epidemiol Biomarkers Prev. 2014, 23 (7): 1340-1345. 10.1158/1055-9965.EPI-14-0035.PubMedPubMedCentralCrossRef
16.
Oliveira-Costa JP, Zanetti JS, Silveira GG, Soave DF, Oliveira LR, Zorgetto VA, Soares FA, Zucoloto S, Ribeiro-Silva A: Differential expression of HIF-1α in CD44+CD24-/low breast ductal carcinomas. Diagn Pathol. 2011, 6: 73-10.1186/1746-1596-6-73. doi:10.1186/1746-1596-6-73PubMedPubMedCentralCrossRef
17.
Fasanella S, Leonardi E, Cantaloni C, Eccher C, Bazzanella I, Aldovini D, Bragantini E, Morelli L, Cuorvo LV, Ferro A, Gasperetti F, Berlanda G, Dalla Palma P, Barbareschi M: Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies. Diagn Pathol. 2011, 6 (Suppl 1): S7-10.1186/1746-1596-6-S1-S7. doi:10.1186/1746-1596-6-S1-S7PubMedPubMedCentralCrossRef
18.
Miyake M, Lawton A, Dai Y, Chang M, Mengual L, Alcaraz A, Goodison S, Rosser CJ: Clinical implications in the shift of syndecan-1 expression from the cell membrane to the cytoplasm in bladder cancer. BMC Cancer. 2014, 14: 86-10.1186/1471-2407-14-86. doi:10.1186/1471-2407-14-86PubMedPubMedCentralCrossRef
19.
Yang N, Feng S, Shedden K, Xie X, Liu Y, Rosser CJ, Lubman DM, Goodison S: Urinary glycoprotein biomarker discovery for bladder cancer detection using LC/MS-MS and label-free quantification. Clin Cancer Res. 2011, 17 (10): 3349-3359. 10.1158/1078-0432.CCR-10-3121.PubMedPubMedCentralCrossRef
20.
Kreunin P, Zhao J, Rosser C, Urquidi V, Lubman DM, Goodison S: Bladder cancer associated glycoprotein signatures revealed by urinary proteomic profiling. J Proteome Res. 2007, 6 (7): 2631-2639. 10.1021/pr0700807.PubMedPubMedCentralCrossRef
21.
Urquidi V, Goodison S, Cai Y, Sun Y, Rosser CJ: A candidate molecular biomarker panel for the detection of bladder cancer. Cancer Epidemiol Biomarkers Prev. 2012, 21 (12): 2149-2158. 10.1158/1055-9965.EPI-12-0428.PubMedPubMedCentralCrossRef
22.
Rosser CJ, Liu L, Sun Y, Villicana P, McCullers M, Porvasnik S, Young PR, Parker AS, Goodison S: Bladder cancer-associated gene expression signatures identified by profiling of exfoliated urothelia. Cancer Epidemiol Biomarkers Prev. 2009, 18 (2): 444-453. 10.1158/1055-9965.EPI-08-1002.PubMedPubMedCentralCrossRef
23.
Aleman A, Cebrian V, Alvarez M, Lopez V, Orenes E, Lopez-Serra L, Algaba F, Bellmunt J, López-Beltrán A, Gonzalez-Peramato P, Cordon-Cardo C, García J, del Muro JG, Esteller M, sánchez-Carbayo M: Identification of PMF1 methylation in association with bladder cancer progression. Clin Cancer Res. 2008, 14 (24): 8236-8243. 10.1158/1078-0432.CCR-08-0778. doi:10.1158/1078-0432.CCR-08-0778PubMedCrossRef
24.
van Oers JM, Zwarthoff EC, Rehman I, Azzouzi AR, Cussenot O, Meuth M, Hamdy FC, Catto JW: FGFR3 mutations indicate better survival in invasive upper urinary tract and bladder tumours. Eur Urol. 2009, 55 (3): 650-657. 10.1016/j.eururo.2008.06.013. doi:10.1016/j.eururo.2008.06.013. Epub 2008 Jun 13PubMedCrossRef
25.
Dyrskjøt L, Zieger K, Kissow Lildal T, Reinert T, Gruselle O, Coche T, Borre M, Ørntoft TF: Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma. Br J Cancer. 2012, 107 (1): 116-122. 10.1038/bjc.2012.215. doi:10.1038/bjc.2012.215. Epub 2012 May 17PubMedPubMedCentralCrossRef
26.
García-Baquero R, Puerta P, Beltran M, Alvarez M, Sacristan R, Alvarez-Ossorio JL, sánchez-Carbayo M: Methylation of a novel panel of tumor suppressor genes in urine moves forward noninvasive diagnosis and prognosis of bladder cancer: a 2-center prospective study. J Urol. 2013, 190 (2): 723-730. 10.1016/j.juro.2013.01.105. doi:10.1016/j.juro.2013.01.105. Epub 2013 Feb 26PubMedCrossRef
27.
Kandimalla R, Masius R, Beukers W, Bangma CH, Orntoft TF, Dyrskjot L, van Leeuwen N, Lingsma H, van Tilborg AA, Zwarthoff EC: A 3-plex methylation assay combined with the FGFR3 mutation assay sensitively detects recurrent bladder cancer in voided urine. Clin Cancer Res. 2013, 19 (17): 4760-4769. 10.1158/1078-0432.CCR-12-3276.PubMedCrossRef
28.
Reinert T, Borre M, Christiansen A, Hermann GG, Ørntoft TF, Dyrskjøt L: Diagnosis of bladder cancer recurrence based on urinary levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 hypermethylation. PLoS One. 2012, 7 (10): e46297-10.1371/journal.pone.0046297. doi:10.1371/journal.pone.0046297. Epub 2012 Oct 3PubMedPubMedCentralCrossRef
29.
Williams SG, Stein JP: Molecular pathways in bladder cancer. Urol Res. 2004, 32 (6): 373-385. 10.1007/s00240-003-0345-y.PubMedCrossRef
30.
Cordon-Cardo C: Molecular alterations in bladder cancer. Cancer Surv. 1998, 32: 115-131.PubMed
31.
Cheng L, Davidson DD, Maclennan GT, Williamson SR, Zhang S, Koch MO, Montironi R, Lopez-Beltran A: The origins of urothelial carcinoma. Expert Rev Anticancer Ther. 2010, 10 (6): 865-880. 10.1586/era.10.73. doi:10.1586/era.10.73PubMedCrossRef
32.
Xu J, Zhu D, Sonoda S, He S, Spee C, Ryan SJ, Hinton DR: Over-expression of BMP4 inhibits experimental choroidal neovascularization by modulating VEGF and MMP-9. Angiogenesis. 2012, 15 (2): 213-227. 10.1007/s10456-012-9254-4. doi:10.1007/s10456-012-9254-4. Epub 2012 Mar 4PubMedPubMedCentralCrossRef
33.
Zhang G, Miyake M, Lawton A, Goodison S, Rosser CJ: Matrix metalloproteinase-10 promotes tumor progression through regulation of angiogenic and apoptotic pathways in cervical tumors. BMC Cancer. 2014, 14: 310-10.1186/1471-2407-14-310. doi:10.1186/1471-2407-14-310PubMedPubMedCentralCrossRef
34.
Tashiro Y, Nishida C, Sato-Kusubata K, Ohki-Koizumi M, Ishihara M, Sato A, Gritli I, Komiyama H, Sato Y, Dan T, Miyata T, Okumura K, Tomiki Y, Sakamoto K, Nakauchi H, Heissig B, Hattori K: Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice. Blood. 2012, 119 (26): 6382-6393. 10.1182/blood-2011-12-399659.PubMedCrossRef
35.
Folkman J: Angiogenesis in cancer, vascular, rheumatoid, and other diseases. Nat Med. 1985, 1: 27-31. 10.1038/nm0195-27.CrossRef
36.
37.
Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996, 86: 353-364. 10.1016/S0092-8674(00)80108-7.PubMedCrossRef
38.
Blood CH, Zetter BR: Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochim Biophys Acta. 1990, 1032: 89-118.PubMed
39.
Miyake M, Goodison S, Lawton A, Gomes-Giacoia E, Rosser CJ: Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway.Oncogene 2014. doi:10.1038/onc.2014.2. [Epub ahead of print].,
40.
Giacoia EG, Miyake M, Lawton A, Goodison S, Rosser CJ: PAI-1 leads to G1-phase cell-cycle progression through cyclin D3/cdk4/6 upregulation. Mol Cancer Res. 2014, 12 (3): 322-334. 10.1158/1541-7786.MCR-13-0543. doi:10.1158/1541-7786.MCR-13-0543. Epub 2014 Jan 24PubMedPubMedCentralCrossRef
41.
Liotta LA, Kleinerman J, Saidel GM: Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res. 1974, 34: 997-1003.PubMed
42.
Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gaspanni G: Tumor angiogenesis: a new significant and independent prognostic indicator in early stage breast carcinoma. J Natl Cancer Inst. 1992, 84: 1875-1887. 10.1093/jnci/84.24.1875.PubMedCrossRef
Metadata
Title
Validation and clinicopathologic associations of a urine-based bladder cancer biomarker signature
Authors
Ge Zhang
Evan Gomes-Giacoia
Yunfeng Dai
Adrienne Lawton
Makito Miyake
Hideki Furuya
Steve Goodison
Charles J Rosser
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2014
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-014-0200-1

Other articles of this Issue 1/2014

Diagnostic Pathology 1/2014 Go to the issue

Research

Association between miR-27a genetic variants and susceptibility to colorectal cancer

Research

InterTan nail versus Gamma3 nail for intramedullary nailing of unstable trochanteric fractures

Research

Berberine inhibits the expression of hypoxia induction factor-1alpha and increases the radiosensitivity of prostate cancer

Research

Association between STAT3 gene Polymorphisms and Crohn’s diseasesusceptibility: a case–control study in a Chinese Han population

Review

Introduction to glycopathology: the concept, the tools and the perspectives

Research

NF-κB signaling and vesicle transport are correlated with the reactivation of the memory trace of morphine dependence