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Open Access Highly Accessed Research article

Investigation of CCL18 and A1AT as potential urinary biomarkers for bladder cancer detection

Makito Miyake1, Shanti Ross1, Adrienne Lawton2, Myron Chang3, Yunfeng Dai3, Lourdes Mengual4, Antonio Alcaraz4, Evan Gomes Giacoia1, Steve Goodison15 and Charles J Rosser156*

Author Affiliations

1 Cancer Research Institute, Orlando Health, Orlando, FL 32827, USA

2 Department of Pathology, Orlando Health, Orlando, FL 32806, USA

3 Department of Biostatistics, University of Florida, Gainesville, FL 32601, USA

4 Laboratory and Department of Urology, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain

5 Nonagen Bioscience Corporation, Orlando, FL 32827, USA

6 Section of Urologic Oncology, 1400 S. Orange Ave., Orlando, FL 32806, USA

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BMC Urology 2013, 13:42  doi:10.1186/1471-2490-13-42

Published: 5 September 2013



In this study, we further investigated the association of two biomarkers, CCL18 and A1AT, with bladder cancer (BCa) and evaluated the influence of potentially confounding factors in an experimental model.


In a cohort of 308 subjects (102 with BCa), urinary concentrations of CCL18 and A1AT were assessed by enzyme-linked immunosorbent assay (ELISA). In an experimental model, benign or cancerous cells, in addition to blood, were added to urines from healthy controls and analyzed by ELISA. Lastly, immunohistochemical staining for CCL18 and A1AT in human bladder tumors was performed.


Median urinary protein concentrations of CCL18 (52.84 pg/ml vs. 11.13 pg/ml, p < 0.0001) and A1AT (606.4 ng/ml vs. 120.0 ng/ml, p < 0.0001) were significantly elevated in BCa subjects compared to controls. Furthermore, the addition of whole blood to pooled normal urine resulted in a significant increase in both CCL18 and A1AT. IHC staining of bladder tumors revealed CCL18 immunoreactivity in inflammatory cells only, and there was no significant increase in these immunoreactive cells within benign and cancerous tissue and no association with BCa grade nor stage was noted. A1AT immunoreactivity was observed in the cytoplasm of epithelia cells and intensity of immunostaining increased with tumor grade, but not tumor stage.


Further development of A1AT as a diagnostic biomarker for BCa is warranted.

Biomarkers; Bladder cancer; Specificity; Urine