Expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer

• We investigated proteins associated with protoporphyrin IX accumulation in bladder cancer cells.
• The expression of FECH showed a negative correlation with PPIX accumulation in vitro.
• The expression of FECH by IHC was correlated with PPIX accumulation in cancer cells.
• The expression of FECH was also correlated with the tumor grade.

BackgroundThe mechanism underlying the increased levels of protoporphyrin IX in bladder cancer remains unclear. Here, we focus on proteins associated with protoporphyrin IX accumulation in bladder cancer cells and investigate the protein that plays a key role in increased protoporphyrin IX accumulation in bladder cancer cells.MethodsWestern blotting was used to determine the expression of peptide transporter 1, hydroxymethylbilane synthase, ferrochelatase, ATP-binding cassette 2, and heme oxygenase-1 in bladder cancer cell line cells. We evaluated the correlation between the expression of each protein and accumulated protoporphyrin IX in these cells using Pearson's correlation analysis. Immunohistochemistry was used to estimate the expression of the same five proteins in samples from 75 patients who underwent transurethral resection of bladder tumors. The correlation between the expression of each protein in cells from resected bladder specimens and accumulated protoporphyrin IX in bladder cancer cells in voided urine was evaluated using Pearson's correlation analysis.ResultsThe expression of ferrochelatase showed a significant negative correlation with protoporphyrin IX accumulation in vitro (p = 0.04). The expression of peptide transporter 1 (p < 0.01, R = 0.39), heme oxygenase-1 (p < 0.01, R = 0.33), and ferrochelatase (p < 0.01, R = 0.75) in resected bladder specimens by immunohistochemistry was correlated with protoporphyrin IX accumulation in bladder cancer cells in voided urine. On multivariate analysis, the expression of ferrochelatase (p = 0.03) was significant factors to predict positive 5-aminolevulinic acid-induced fluorescent cytology.ConclusionThe expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer.