Candidate biomarkers predicting clinical outcome after hyperbaric oxygen against chronic radiation cystitis

Abstract Background Hyperbaric oxygen (HBO2) is effective against radiation cystitis. In this exploratory analysis we employed proteomics to assess biomarkers predicting clinical efficacy and the pharmacodynamics of HBO2 in radiation cystitis. Methods Global quantitative proteomics was performed on biopsies taken before and after HBO2 in patients with radiation cystitis from the RICH-ART trial (NCT01659723). The proteome of HBO2 responders (R) was compared to non-responders (NR) and between R and NR at baseline. Immunohistochemistry was employed to assess the expression of potential biomarkers in urinary bladder biopsies. Biological processes were identified by using the STRING database. Results Among proteins more expressed in R than NR at baseline were neutrophil defensin 1 and less expressed were chymase and mast cell carboxypeptidase A (CPA3). Among processes differentiating R from NR at baseline were processes regulating translation and complement activation. The top enriched biological processes in NR after HBO2 were processes regulating antigen processing and presentation. Only a few processes were affected by HBO2 in responders. No significant differences in the number of chymase+, CPA3 + and tryptase+ mast cells were observed in bladder specimens between R and NR before and after HBO2. The staining intensity of tryptase, chymase, CPA3 and complement factors C3, C4 and C8 were similar between R and NR and after HBO2. Conclusions Multiple processes regulating the immune system, complement activation and translation in radiation cystitis are changed after HBO2. However, only a few processes were associated with the clinical efficacy of HBO2. The involvement of mast cells in the pathogenesis of radiation cystitis is suggested.