AIMS: Gene expression profiling of Bladder biopsies in patients with interstitial cystitis/Bladder pain syndrome (IC/BPS), typically obtained following therapeutic Bladder hydrodistention (HOD), is used to improve our understanding of molecular phenotypes. The objective of this study was to determine if the HOD procedure itself impacts the biopsy gene expression profile and, by extension, whether biopsies from non-HOD bladders are appropriate controls. METHODS: Bladder biopsies were obtained just before HOD and immediately following HOD from 10 consecutively recruited IC/BPSpatients undergoing therapeutic HOD. Biopsies were also obtained from four non-IC/BPSpatients who did not undergo HOD (controls). Total RNA was isolated from each of the 24 samples and used to query whole-genome microarrays. Differential gene expression analysis was performed to compare expression profiles of IC/BPS biopsies before and after HOD, and between IC/BPS and control biopsies. RESULTS: Principal component analysis revealed complete separation between gene expression profiles from IC/BPS and control samples (q ≤ 0.05) and while IC/BPS samples before and after HOD showed no significant differences in expressed genes, 68 transcripts were found to be significantly different between IC/BPS and control samples (q ≤ 0.05). CONCLUSIONS: The Bladder HOD procedure itself does not significantly change gene expression within the IC/BPSpatientBladder, a finding that provides evidence to support the use of biopsies from non-IC/BPSpatients that have not undergone HOD as controls for gene expression studies.
Keay SK , Birder LA , Chai TC . Evidence for bladder urothelial pathophysiology in functional bladder disorders. BioMed Res Int. 2014;2014:1-15. https://doi.org/10.1155/2014/865463
Liu HT , Kuo HC . Increased urine and serum nerve growth factor levels in interstitial cystitis suggest chronic inflammation is involved in the pathogenesis of disease. PLoS One. 2012;7(9):e44687. https://doi.org/10.1371/journal.pone.0044687
Ener K , Keske M , Aldemir M , et al. Evaluation of oxidative stress status and antioxidant capacity in patients with painful bladder syndrome/interstitial cystitis: preliminary results of a randomised study. Int Urol Nephrol. 2015;47(8):1297-1302. https://doi.org/10.1007/s11255-015-1021-1
Lee JD , Lee MH . Increased expression of hypoxia-inducible factor-1α and vascular endothelial growth factor associated with glomerulation formation in patients with interstitial cystitis. Urology. 2011;78(4):971. https://doi.org/10.1016/j.urology.2011.05.050
Kiuchi H , Tsujimura A , Takao T , et al. Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations. BJU Int. 2009;104(6):826-831. https://doi.org/10.1111/j.1464-410X.2009.08467.x
Hanno PM , Burks DA , Clemens JQ , et al. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011;185(6):2162-2170. https://doi.org/10.1016/j.juro.2011.03.064
Ens G , Garrido GL . Role of cystoscopy and hydrodistention in the diagnosis of interstitial cystitis/bladder pain syndrome. Transl Androl Urol. 2015;4(6):624-628. https://doi.org/10.3978/j.issn.2223-4683.2015.09.0
Kim A , Han JY , Ryu CM , et al. Histopathological characteristics of interstitial cystitis/bladder pain syndrome without Hunner lesion. Histopathology. 2017;71(3):415-424. https://doi.org/10.1111/his.13235
Colaco M , Koslov DS , Keys T , et al. Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome. J Urol. 2014;192(4):1123-1129. https://doi.org/10.1016/j.juro.2014.05.047
Tyagi P , Moon CH , Janicki J , et al. Recent advances in imaging and understanding interstitial cystitis. F1000Res. 2018;7:F1000. https://doi.org/10.12688/f1000research.16096.1
Keay S , Kleinberg M , Zhang CO , Hise MK , Warren JW . Bladder epithelial cells from patients with interstitial cystitis produce an inhibitor of heparin-binding epidermal growth factor-like growth factor production. J Urol. 2000;164(6):2112-2118.
Uhlen M , Fagerberg L , Hallstrom BM , et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419. https://doi.org/10.1126/science.1260419
Chaqour B , Whitbeck C , Han JS , et al. Cyr61 and CTGF are molecular markers of bladder wall remodeling after outlet obstruction. Am J Physiol Endocrinol Metab. 2002;283(4):E765-E774. https://doi.org/10.1152/ajpendo.00131.2002
Kireeva ML , Latinkić BV , Kolesnikova TV , et al. Cyr61 and Fisp12 are both ECM-associated signaling molecules: activities, metabolism, and localization during development. Exp Cell Res. 1997;233(1):63-77. https://doi.org/10.1006/excr.1997.3548
Matika CA , Wasilewski M , Arnott JA , Planey SL . Antiproliferative factor regulates connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells. Mol Biol Cell. 2012;23(10):1976-1985. https://doi.org/10.1091/mbc.E11-08-071
Murphy-Ullrich JE . Thrombospondin 1 and its diverse roles as a regulator of extracellular matrix in fibrotic disease. J Histochem Cytochem. 2019;67(9):683-699. https://doi.org/10.1369/0022155419851103
Parsons CL . The role of a leaky epithelium and potassium in the generation of bladder symptoms in interstitial cystitis/overactive bladder, urethral syndrome, prostatitis and gynaecological chronic pelvic pain. BJU Int. 2011;107(3):370-375. https://doi.org/10.1111/j.1464-410X.2010.09843.x
Birder LA , Hanna-Mitchell AT , Mayer E , Buffington CA . Cystitis, co-morbid disorders and associated epithelial dysfunction. Neurourol Urodyn. 2011;30(5):668-672. https://doi.org/10.1002/nau.21109
Lai HH , Pickersgill NA , Vetter JM . Hunner lesion phenotype in interstitial cystitis/bladder pain syndrome: a systematic review and meta-analysis. J Urol. 2020;204(3):518-523. https://doi.org/10.1097/JU.0000000000001031
Whitmore KE , Fall M , Sengiku A , Tomoe H , Logadottir Y , Kim YH . Hunner lesion versus non-Hunner lesion interstitial cystitis/bladder pain syndrome. Int J Urol. 2019;26(Suppl 1):26-34. https://doi.org/10.1111/iju.13971
Akiyama Y , Hanno P . Phenotyping of interstitial cystitis/bladder pain syndrome. Int J Urol. 2019;26(Suppl 1):17-19. https://doi.org/10.1111/iju.13969
Mahendru AA , Al-Taher H . Cystodistension: certainly no standards and possibly no benefits-survey of UK practice. Int Urogynecol J. 2010;21(2):135-139. https://doi.org/10.1007/s00192-009-1026-3
Hoke TP , Goldstein H , Saks EK , Vakili B . Hydrodistention of the bladder for the treatment of bladder pain syndrome/interstitial cystitis (BPS/IC). Neurourol Urodyn. 2017;36(3):784-786. https://doi.org/10.1002/nau.23024