title: Investigation of CCL18 and A1AT as potential urinary biomarkers for bladder cancer detection.
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.
authors.affiliation: Cancer Research Institute, Orlando Health, Orlando, FL 32827, USA. deacdoc@aol.com.
authors.forename: Makito
authors.initials: M
authors.lastname: Miyake
authors.forename: Shanti
authors.initials: S
authors.lastname: Ross
authors.forename: Adrienne
authors.initials: A
authors.lastname: Lawton
authors.forename: Myron
authors.initials: M
authors.lastname: Chang
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Dai
authors.forename: Lourdes
authors.initials: L
authors.lastname: Mengual
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcaraz
authors.forename: Evan Gomes
authors.initials: EG
authors.lastname: Giacoia
authors.forename: Steve
authors.initials: S
authors.lastname: Goodison
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D019742:Chemokines, CC / Q000652:urine*; D005240:Feasibility Studies; D005260:Female; D005431:Florida / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine*; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; C111792:CCL18 protein, human; D019742:Chemokines, CC; D000515:alpha 1-Antitrypsin