The proteomic landscape shows oncologic relevance in cystitis glandularis

Background: The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear. Methods: We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation. Results: We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG. Conclusions: Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.