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

Makito Miyake, Shanti Ross, Adrienne Lawton, Myron Chang, Yunfeng Dai, Lourdes Mengual, Antonio Alcaraz, Evan Gomes Giacoia, Steve Goodison, Charles J. Rosser

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background: 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. Methods. 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. Results: 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. Conclusions: Further development of A1AT as a diagnostic biomarker for BCa is warranted.

Original languageEnglish (US)
Article number42
JournalBMC Urology
Volume13
DOIs
StatePublished - 2013

Keywords

  • Biomarkers
  • Bladder cancer
  • Specificity
  • Urine

ASJC Scopus subject areas

  • Reproductive Medicine
  • Urology

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    Miyake, M., Ross, S., Lawton, A., Chang, M., Dai, Y., Mengual, L., Alcaraz, A., Giacoia, E. G., Goodison, S., & Rosser, C. J. (2013). Investigation of CCL18 and A1AT as potential urinary biomarkers for bladder cancer detection. BMC Urology, 13, [42]. https://doi.org/10.1186/1471-2490-13-42