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

Diagnostic Pathology

Charles J Rosser⁵  Steve Goodison⁴  Hideki Furuya⁵  Makito Miyake³  Adrienne Lawton¹  Yunfeng Dai²  Evan Gomes-Giacoia³  Ge Zhang³ 

[1] Department of Pathology, Orlando Health, Orlando, FL, USA;Department of Biostatistics, The University of Florida, Gainesville, Florida, USA;MD Anderson Cancer Center Orlando, Cancer Research Institute, Orlando, Florida, USA;Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA;University of Hawaii Cancer Center, 701 Ilalo St, Rm 327, Honolulu 96813, HI, USA

关键词: Stage;    Signature;    Grade;    Diagnosis;    Bladder cancer;   

Others  :  1149355
DOI  :  10.1186/s13000-014-0200-1

 received in 2014-08-12, accepted in 2014-10-08,  发布年份 2014

【 摘 要 】

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.diagnosticpathology.diagnomx.eu/vs/13000_2014_200 webcite

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 2012, 62(1):10-29.
• [2]Aben KK, Kiemeney LA: Epidemiology of bladder cancer. Eur Urol 1999, 36:660-672.
• [3]Hall MC, Chang SS, Dalbagni G, Pruthi RS, Seigne JD, Skinner EC, Wolf JS Jr, 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.
• [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.
• [5][http://www.seer.cancer.gov/csr/1975_2002] webcite Surveillance, Epidemiology, and End Results Program. Available at: . Accessed June 22, 2013.
• [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. doi:10.1016/j.eururo.2011.03.023. Epub 2011 Mar 23. Review
• [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. Review
• [8]Urquidi V, Goodison S, Rosser CJ: Diagnostic potential of urinary 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. Epub 2012 May 21
• [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. BioMed Central Full Text
• [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. Epub 2012 Mar 3
• [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.
• [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. doi:10.1016/j.juro.2013.06.011
• [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.
• [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.
• [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-1? in CD44+CD24-/low breast ductal carcinomas. Diagn Pathol 2011, 6:73. doi:10.1186/1746-1596-6-73 BioMed Central Full Text
• [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. doi:10.1186/1746-1596-6-S1-S7 BioMed Central Full Text
• [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. doi:10.1186/1471-2407-14-86 BioMed Central Full Text
• [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.
• [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.
• [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.
• [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.
• [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. doi:10.1158/1078-0432.CCR-08-0778
• [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. doi:10.1016/j.eururo.2008.06.013. Epub 2008 Jun 13
• [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. doi:10.1038/bjc.2012.215. Epub 2012 May 17
• [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. doi:10.1016/j.juro.2013.01.105. Epub 2013 Feb 26
• [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.
• [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. doi:10.1371/journal.pone.0046297. Epub 2012 Oct 3
• [29]Williams SG, Stein JP: Molecular pathways in bladder cancer. Urol Res 2004, 32(6):373-385.
• [30]Cordon-Cardo C: Molecular alterations in bladder cancer. Cancer Surv 1998, 32:115-131.
• [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. doi:10.1586/era.10.73
• [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. doi:10.1007/s10456-012-9254-4. Epub 2012 Mar 4
• [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. doi:10.1186/1471-2407-14-310 BioMed Central Full Text
• [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.
• [35]Folkman J: Angiogenesis in cancer, vascular, rheumatoid, and other diseases. Nat Med 1985, 1:27-31.
• [36]Folkman J, Klagsbrun M: Angiogenic factors. Science 1987, 235:442-447.
• [37]Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996, 86:353-364.
• [38]Blood CH, Zetter BR: Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochim Biophys Acta 1990, 1032:89-118.
• [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. doi:10.1158/1541-7786.MCR-13-0543. Epub 2014 Jan 24
• [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.
• [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.