A Urine-Based Biomarker for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

A Retrospective Multi-Center Study

Weining Liang; Zhigang Wu; Guowei Zhang; Weikang Chen; Xiangnong Hu; Jianjun Yang; Jie Meng; Yan Zeng; Hongjun Li; Xuejun Shang


Transl Androl Urol. 2020;9(5):2218-2226. 

In This Article

Abstract and Introduction


Background: Chronic prostatitis (CP) or chronic pelvic pain syndrome (CPPS) is one of the most common diseases in young and middle-aged men, accounting for 30% of outpatient men in urology OPD. There are no definitive diagnostic criteria for CP or CPPS and no accepted therapies that cure the disease.

Methods: We identified 372 patients with CP diagnosed from 2015 to 2018 and collect the information of age, routine urinary test, express prostatic secretion (EPS), and NIH-Chronic Prostatitis Symptom Index (NIH-CPSI).

Results: Our study proved a correlation between the increase of prostatic exosomal proteins (PSEPs) level and NIH-CPSI scores. Spearman's correlation coefficient showed a significant level correlation between NIH-CPSI and PSEP level (rs=0.194, P=0.0035). In the meantime, the correlation was found between the PSEP level and EPS-white blood cells. Spearman's correlation coefficient showed that there was a significant hierarchical correlation between EPS-white blood cells and PSEP level (rs=0.183, P=0.001).

Conclusions: These findings highlight the potential of PSEP is a practical indicator of the symptomatic progression of CP/CPPS. Applications of PSEP assay may guide drug discovery and lead to better treatment to improve the patient's quality of life. All in all, PSEP detection in urine is safe and effective, and it is worthy of further promotion and application in clinical practice.


Chronic prostatitis (CP) or chronic pelvic pain syndrome (CPPS) is one of the most common diseases in young and middle-aged men and accounts for up to 30% of the outpatient male observed in the urological clinics.[1] From the epidemiological survey, 4.5–10% of the male population presents symptoms of prostatitis worldwide, and 50% of men have prostatitis at some points during their lifetime.[2,3] Thus, CP/CPPS is of paramount importance as a medical problem for health care internationally. However, despite the intense research in the past decades, the etiology and pathogenesis of CP/CPPS are still unclear. Also, the clinical manifestation of CP/CPPS lacks specificity, making clinical diagnosis and treatment challenging.[4,5] The cause of CPPS has not yet been clarified, but the basic viewpoint is: CP/CPPS is a complex disease involving physical and mental factors. Even if there are obvious physical lesions that can cause pelvic pain, psychological and social factors cannot be ignored. Treatment requires the use of a multidisciplinary and comprehensive approach, including surgery, drugs, physiotherapy, psychotherapy, etc..[6] The purpose of treatment is to relieve pain, improve function and eliminate psychological barriers. Many biomarkers have also been confirmed to be involved in inflammation.[7] So the research of biomarkers is not only helpful for the accurate diagnosis of CP/CPPS, but also for the development of new targeted drugs for CP/CPPS, which is important for the individualized and precise treatment of CP/CPPS.

The diagnosis of CP/CPPS has included a combined process of recording clinical symptoms and signs, routine urine tests, or culture and the express prostatic secretion (EPS), which can be retrieved by performing a rectal exam with a massage on the prostate.[8] However, this is a clinical process that requires a qualified doctor to operate and often disturb the patients. Also, the EPS index may exclude other potential pelvic pain associated with urological disorders. There is a lack of effective tools for the evaluation of the disease and the judgment of effect. At present, the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) is a questionnaire most commonly used internationally. It was developed by experts organized by the National Institutes of Health. Most practice clinics and hospitals in our country (for example, the Jinling hospital in Nanjing; the Taicang People's Hospital and Military General Hospital in Jinan) carry out the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) to document the patient symptoms and responses to diagnose CP/CPPS. In this process, the patient must answer several questions. The doctor should calculate the NIH-CPSI score according to medical history and clinical symptoms. Therefore, it is imperative to find and introduce a valid tool of CP/CPPS surrogate for diagnosis.

Also, studies have shown increased risks of prostate cancer (PCa) for men with a history of prostatitis compared with the case-control. For example, Tomas et al. found the atypical hyperplasia in epithelial cells with dark, swelling, and prominent nucleoli in the tissue slide showing a lesion of inflammatory atrophy. Inflammatory atrophy can supply a favorable breeding ground for PCa development.[9]

Exosomes are small, membrane-bound storage vesicles that mediate transport of a cytosolic cargo between the cells and to the extracellular space.[10] Exosomes are produced in many cell types, including the prostate epithelial cells, where they are termed prostasomes.[11] They can also be excreted to the interstitial tissue compartments when infiltrating leukocytes accumulate in response to inflammation. Thus, prostasomes can be found in seminal plasma, and urine.[12] Prostasomes have been reported to elicit antioxidant effects, antibacterial activity, and immunomodulation.[13,14] It has been proposed prostasomes may reduce the production of reactive oxygen species (ROS).[15] Studies also suggested prostasomes inhibit the NADPH oxidase activity of polymorph nuclear neutrophils by lipid transfer from prostasomes to the plasma membrane of these cells.[16] The molecular composition of human prostasomes is varied and comprises hundreds of known and unknown proteins. Prostate diseases, including prostate cancer, benign prostatic hyperplasia (BPH), and prostatitis, present unique phenotypes at the level of their respective proteasomal proteomes.[17]

Recently, antibodies against human prostasomes were generated and found to be reactive to urine samples of CP/CPPS patients. The proteins that are immune reactive to the antibodies are appointed as prostatic exosomal proteins (PSEPs).[18,19]

A multi-center clinical trial performed in China showed that CP/CPPS patients present elevated PSEP in the void urine when compared to the healthy men.[20] Subsequent applications of the PSEP test confirmed the utility in many clinics across China; however, these applications have not addressed the relationship between PSEP test and current methods of diagnosing CP/CPPS. In this study, we intended to be the first to reveal the potential relationship between PSEP in urine samples and EPS indexes, including white blood cells (WBC) and lecithin corpuscles and NIH-CPSI. Our studies highlight the potential value of PSEP as an indicator for CP/CPPS symptoms and disease progression.

We present the following article in accordance with the MDAR reporting checklist (available at http://dx.doi.org/10.21037/tau-20-1268).