Baseline Bladder Proteins May Predict Hyperbaric Oxygen Response in Radiation Cystitis

In an exploratory proteomics investigation evaluating patients with radiation cystitis, researchers have identified distinct baseline protein expressions and biological processes that differentiate individuals who respond clinically to hyperbaric oxygen therapy from those who do not. The global quantitative analysis revealed that bladder tissue from patients who responded to treatment exhibited higher baseline expression of neutrophil defensin 1 compared to non-responders. In contrast, patients who failed to respond clinically showed higher baseline levels of chymase and mast cell carboxypeptidase A, also designated CPA3. These molecular patterns establish candidate predictive biomarkers for hyperbaric oxygen efficacy in chronic radiation cystitis before therapy begins.

The exploratory study utilized clinical specimens collected from patients participating in the RICH-ART clinical trial, identified in trial registries as NCT01659723. While hyperbaric oxygen, denoted as HBO2, is recognized as effective against radiation cystitis, the biological mechanisms and molecular markers governing patient responses remain incompletely characterized. To address this knowledge gap, the research team employed proteomics to assess biomarkers capable of predicting clinical efficacy as well as the pharmacodynamics of hyperbaric oxygen therapy. The investigators conducted their global quantitative proteomic analysis directly on urinary bladder biopsies harvested from patients both before undergoing HBO2 treatment and after completing the therapeutic course.

To delineate the functional pathways involved, the researchers performed systematic comparisons between the proteome of hyperbaric oxygen responders and non-responders, focusing on differences observed both at baseline and post-treatment. Biological processes associated with the altered proteins were systematically categorized and identified through analysis with the STRING database. Among the major biological processes that differentiated responders from non-responders at baseline were pathways regulating cellular translation alongside pathways regulating complement activation. These baseline distinctions demonstrate that specific immunological and translational mechanisms distinguish the bladder tissue of future responders from non-responders prior to hyperbaric oxygen exposure.

Following hyperbaric oxygen therapy, the proteomic alterations observed within bladder tissue differed notably between the clinical outcome groups. In patients classified as non-responders, the top enriched biological processes detected after hyperbaric oxygen treatment were processes regulating antigen processing and presentation. In stark contrast, only a few biological processes were affected by hyperbaric oxygen therapy in patients who experienced a positive clinical response. This disparity suggests that the overall pharmacodynamic impact of hyperbaric oxygen on bladder tissue involves distinct molecular responses depending on whether a patient achieves clinical improvement.

Alongside global proteomics, the investigators employed immunohistochemistry to assess the localized tissue expression of potential protein biomarkers within the urinary bladder biopsies. The team specifically evaluated the presence and distribution of mast cells expressing chymase, CPA3, and tryptase. Their evaluation found no statistically significant differences in the number of chymase-positive, CPA3-positive, or tryptase-positive mast cells in bladder specimens when comparing responders to non-responders either before therapy or after hyperbaric oxygen treatment. Moreover, quantitative evaluation of staining intensity for tryptase, chymase, CPA3, and complement factors C3, C4, and C8 demonstrated similar levels between responders and non-responders, with no significant differences emerging after hyperbaric oxygen therapy.

Based on these findings, the authors concluded that hyperbaric oxygen therapy alters multiple biological processes regulating the immune system, complement activation, and translation in radiation cystitis. Nevertheless, despite widespread changes across these functional networks, only a few specific processes demonstrated a direct association with the actual clinical efficacy of hyperbaric oxygen. The investigators noted that the differential expression of chymase and mast cell carboxypeptidase A at baseline, considered together with the tissue staining observations, suggests the involvement of mast cells in the underlying pathogenesis of radiation cystitis.

Subject of Research: Candidate proteomic biomarkers for hyperbaric oxygen therapy in radiation cystitis

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

Article References: Giglio, D., Sallam, L., Thorsell, A., Mölne, J., Oscarsson, N., & Seeman-Lodding, H. (2026). Candidate biomarkers predicting clinical outcome after hyperbaric oxygen against chronic radiation cystitis. BMC Cancer. https://doi.org/10.1186/s12885-026-17309-z

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17309-z

Keywords: radiation cystitis, hyperbaric oxygen, proteomics, biomarkers, RICH-ART trial, neutrophil defensin 1, mast cells, complement activation, Candidate, predicting, clinical, outcome