NIH category III prostatitis is the most common type of chronic prostatitis, patients always have chronic pelvic pain symptoms and possibly voiding symptoms in the absence of urogenital infections[23], which has a significant negative impact on the quality of life. The etiology of most CP/CPPS cases is uncertain, and the controversial cause is that CP/CPPS may be in virtue of infections like bacteria, viruses[23, 24]. K Wenninger stated that the sickness of chronic prostatitis patients similar to the patients suffering myocardial infarction, angina or Crohn's disease, according to their sickness impact profile mean total score, which is within the range of scores of those diseases reported in the literature[25]. And it was reported that prevalence of sexual dysfunction in Chinese men with chronic prostatitis has a negative correlation with age, and the duration of chronic prostatitis (all P < 0.01)[26], several studies also considered that CP/CPPS might be related to the development of prostate cancer[27, 28]. Furthermore, because of the accompanied calcification, the effective treatment of category III prostatitis is difficult. CP/CPPS has seriously affected the quality of males’ life. In view of previous studies, trace metals play an increasingly important role in the development of prostatitis, for instance, Zn[29, 30]. Therefore, we perform this study to reveal the difference between concentrations of Cu, Zn, Ca, Mg in healthy controls compared to the patients with CP/CPPS, providing fundamental basis for clinical diagnosis.
In our study, Zn was significantly changed. It is an essential trace element, required for maintenance of structural integrity and DNA binding activity in over 2,000 transcription factors [31]. It has been reported that human seminal plasma contains high concentrations of Zn, almost secreted by prostate gland[32]. It plays a momentous physiological and pathogenesis role in male’s health, and is necessary for preserving the lining of the reproductive organs, could have regulating action in the progress of capacitation and acrosome reaction, the lack of Zn may affect weakening of immune and reproductive system[33]. In addition, Paola Bonaventura indicated that acute Zn deficiency could cause a decrease in innate and adaptive immunity, and chronic deficiency might increase inflammation[34]. In our previous study and present study, we found EPS Zn level are higher in the healthy controls than it in CP/CPPS[35], indicating that EPS Zn deficiency may cause the occurrence of chronic prostatitis, but the specific mechanism still needs to be explored in depth. Nowadays, biologic Zn therapy is positively effective on sperm motility and the use of biologic Zn supplementation is an efficient way for the treatment of infertile males with chronic prostatitis[36]. In addition, we also found serum Zn level appears to be higher in category IIIa prostatitis, although no direct evidence showed that chronic prostatitis is related to prostate cancer, the level of serum Zn had been reported to be positively associated with prostate cancer risk[37]. Also, many researchers have confirmed that Zn2+ is significantly positively correlated with the risk of prostate cancer[37], When the concentration of Zn2+ and zinc transporter ZIP1 in the body is down-regulated, it is often accompanied by the oncogenic genetic transformation of prostate cells from a normal state to a tumor state with malignant potential[38]. Therefore, we think it is still valuable to further study the role of Zn level between chronic prostatitis and prostate cancer.
The next interesting metal is Cu. Cu is an essential cofactor or a structural component in a number of meaningful enzymes, such as Cu/Zn superoxide dismutase (SOD1), which has functions in superoxide detoxification and signaling[39]. However, the over-loaded copper in a free state can trigger the production of a large number of free radicals, leading to the destruction of protein and DNA, and causing the inflammatory changes or even cancer in cells[40, 41]. Our previous study suggested that superoxide dismutase 3 (SOD3) containing catalytic copper and structural inc ions in their active sites is significantly higher in all types of prostatitis than in the control, and is a potential diagnostic marker of nonbacterial prostatitis[35, 39]. O A Adaramoye et al. also reported that the levels of whole blood superoxide dismutase (SOD) was significantly lower (p < 0.05) in the PCa patients[42]. So we speculated that the increase of Cu may be one of the pathogenesis of category III prostatitis, and the prostatitis even cancer may be developed by effecting the expression of these Cu related proteins. In this data, the concentration of EPS Cu had a marked increase only in category IIIb prostatitis and the AUC of EPS Cu, Cu/Ca for predicting category IIIb prostatitis are greater than 0.88 (P < 0.0001), indicating that Cu could be a useful factor in category IIIb prostatitis.
Ca and Mg were analyzed in this study as well. Their EPS concentrations were reduced sharply and positively correlated with EPS Zn level in both category IIIa and IIIb prostatitis. Chang-Sheng Zhan et al. found that calcium/calmodulin-dependent kinase Ⅳ (CaMK4) was increased in the Th17 cells of experimental autoimmune prostatitis, which was activated by intracellular cytosolic Ca2+, Ca2+ -CaMK4-Akt/mTOR-IL-17A axis inhibition may serve as a promising therapeutic strategy for CP/CPPS[10]. Few studies explore the relationship between Ca, Mg level and CP/CPPS directly. C Y Yang etc. investigated the possible association between the increased risk of prostate cancer and the concentrations of Ca and Mg in drinking water from municipal supplies, and they found that the relationship between Ca levels in drinking water and prostate cancer were not statistically clear while Mg intake from drinking water and other dietary sources may has a significant protective effect against the risk of prostate cancer development[43]. Besides, both EPS and serum Ca, Mg had a higher AUC for predicting category IIIa and IIIb prostatitis. Although we have obtained some great discoveries through this study, some limitations are still obvious. The total samples are small, and all samples were collected from patients who attended the healthy physical examination in the Guilin area in Guangxi, China, and the results could not be extrapolated to the whole population reliably, and in the future, more samples should be detected in our research. Based on results above, further learning the function of these metals in category III prostatitis is important, and the specific role of these metals related proteins may also have potential research value.