Wisconsin Urologic Research Institute
Petra Popovics, PhD (this will link to your DOU profile)
Lower urinary tract symptoms develop in the majority of men with advanced age primarily due to pathological changes in the prostate gland. Pharmacological treatments for LUTS focus on the reversion of prostatic enlargement and the reduction of smooth muscle tone as these factors are considered to instigate LUTS. However, patients may not respond or become resistant to these therapies which suggests a different pathological process to be responsible for symptoms at least in a subset of BPH patients.
Prostatic fibrosis has recently emerged as a potential contributor to LUTS by causing tissue stiffness and increased urethral resistance. Fibrosis is associated with LUTS, but there is little information on how it contributes to symptoms and there are no non-invasive detection strategies to identify patients with progressed stage of this condition who would benefit the most from anti-fibrotic therapies.
Previous studies from the UW-Madison DOU identified potential urinary biomarkers related to collagen metabolism and fibrotic diseases, such as hydroxyproline, Timp1, Scnn1g, Prdx2, Park7 and Col14a1. These markers have not yet been tested for correlation with the degree of prostate tissue fibrosis or symptom score. The goal of our study is to identify the symptomology that is associated with prostatic fibrosis and test potential urinary biomarkers that could serve as diagnostic tools to determine the degree of fibrosis in the prostate.
In Aim1, we will develop a LUTS data and specimen repository by recruiting 100 patients who are referred to prostate surgery to relieve LUTS symptoms at UW or Meriter Hospital. Surgeries include Holmium Laser Enucleation of the Prostate (HoLEP) and Transurethral Resection of the Prostate (TURP) performed by Drs. Dan Gralnek, Christopher Manakas or Matthew Grimes. Our approved IRB protocol allows the collection of resected prostate tissue directly from the OR and urine and serum from recruited patients along with symptom score and chart review. Aim2 will assess the level of overall fibrosis in the collected tissues using the collagen-metabolite, hydroxyproline, as marker. Patients will be divided into 3 subgroups based on tissue hydroxyproline levels and IPSS symptom score will be correlated with the degree of prostatic fibrosis. Aim3 will determine the level of previously established markers TIMP1, hydroxyproline and others, in urine samples and determine their correlation with tissue levels of fibrosis.
Our study will provide biomarkers to allow non-invasive determination of fibrotic grade in the prostate. This will be essential to develop diagnostic testing and for the design of human clinical trials involving new anti-fibrotic therapies. As part of the study, we will develop a LUTS specimen and data repository that can be utilized for subsequent studies by investigators of the DOU, especially for studies where direct association of patient data with tissue, serum and urine measurement is essential. In addition, various anti-fibrotic therapies are currently being tested in the pre-clinical setting to target prostatic fibrosis without possessing a tool to identify patients with high-grade fibrotic disease who would primarily benefit from these therapies.