Some of the main purposes of cancer research are to facilitate diagnosis methods, increase predictiveness and develop non-invasive screening methods. Serum PSA levels may be detected on highly varying levels in bacterial prostatitis. Many studies have reported that an elevated PSA level is related to prostatitis. Screening for prostate cancer with serum prostate-specific antigen (PSA) aims to detect prostate cancer at an early, intervenable stage amenable to curative treatment and reduction in overall and disease-specific mortality. However, the evidence has so far not demonstrated that screening for prostate cancer saves lives [12, 13].
A member of the cathelicidins family, LL-37, has a peptide structure and is one of the elements of the immune system in addition to its anti-tumoral and anti-microbial effects. Previous studies have shown that LL-37 was expressed in tumor tissue in prostate carcinoma as in many cancer types and asserted that it could be related to the progression of the disease . Many studies reported that serum LL-37 levels were detected to be higher than normal in the progression of diseases with chronic inflammation or in autoimmune diseases .
In the histopathological examinations on the prostate carcinoma patients, multifocal acute and chronic inflammation areas were observed especially in the regions not infiltrated by the tumor and were histologically benign. Acute inflammation of the prostate gland is characterized by infiltration of neutrophil leukocytes, and epithelial damage chronic inflammation is manifested with lymphocyte and macrophage reaction surrounding atrophic prostatic glands . The etiology of this typical prostatic inflammation is not yet known. However, similar findings are observed also in the Helicobacter pylori infection of the stomach, and this situation has a relationship with inflammation, gastric atrophy and then gastric carcinoma. It was asserted that there could be such an infectious etiology also for prostate carcinoma. Although there is no microbiological agent clearly shown to cause prostate carcinoma development, there are scientific data which suggest that the inflammatory process has an important role in prostatic carcinogenesis . Numerous inflammatory mediators have been implicated in cancer metastasis such as interleukin-6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-α) .
No previous study was found about measurement of serum LL-37 levels in patients with prostate carcinoma or prostatitis. In the study conducted by Persson et al. about chronic obstructive pulmonary disease, an evident example of a similar chronic inflammation, it was found that the LL-37 levels were related to inflammation severity and bacterial colonization . In their study on chronic viral hepatitis patients, Iacob et al. similarly detected LL-37 levels to be significantly higher in the active form of the disease . In their study, Majewski et al. compared patients with acute pneumonia and pulmonary tuberculosis and showed that serum LL-37 levels were significantly higher in the pulmonary tuberculosis patients .
Although it is known that prostatitis etiology is not always bacterial or viral, it was observed that LL-37 levels are higher with respect to acute diseases as the inflammation becomes more chronic. Nielsen et al. studied urine LL-37 levels regarding urinary infections on female patients, and urinary system infections were found to correlate with urine LL-37 levels . Sensitivity against LL-37 was found to be lower in fecal Escherichia coli isolates observed in the patient group. In this study, it was stated that LL-37 concentration in the urinary tract and low sensitivity to LL-37 may increase the possibility of urinary tract infections . Hensel et al. investigated LL-37 expression in cell culture series in human and animal prostate tumor tissues using both the immunohistochemical method and polymerase chain reaction. They found that LL-37 expression was related to tumor angiogenesis, proliferation and invasion . They asserted that LL-37 could be a potential new treatment goal for prostate carcinoma.
Cha et al. showed that in prostate cancer progression LL-37 mediated the differentiation of myeloid progenitors in the microvicinity to M2 macrophages and thus promoted tumor development. In their study, they also determined that tumor progression was inhibited when LL-37 expression was downregulated from prostate tumors . In this study, it was shown that serum LL-37 levels could be both diagnostic and a guide in disease progression.
In our study, there was no statistically significant difference in the LL-37 serum levels between the prostatitis patient group and the healthy group (p = 0.02). Examining the other results of the study, the serum LL-37 level was higher in the prostate carcinoma patients with respect to the control group (p = 0.004). The fact that, in our study, the serum LL-37 levels of the prostate carcinoma patients were higher than the healthy group and there was no difference with the prostatitis group, could be explained with the inflammation, invasion or metastasis status of the tumors. We found that the cutoff values for LL37 serum level were 3.5151 ng/mL to differentiate prostate cancer from prostatitis, 2.2620 ng/mL to differentiate prostate cancer from control group (suggesting that a LL37 value above this threshold might indicate greater odds of inflammation and hence prostate cancer) and 1.2340 ng /mL to differentiate prostatitis from control group (meaning that a LL37 value above this threshold can indicate an increased likelihood of having a prostatitis).
Our study has a number of limitations. Firstly, the sample size was small. Secondly, our study did not involve a comparison of urinary LL37 levels in a different cancer.
Our study has a number of limitations. In particular, small sample size is an important limitation and may have precluded demonstration of less clear associations between studied variables.
Our study was the first study where serum LL-37 levels in prostate carcinoma and prostatitis patients were compared to a healthy group. In the future studies, we might plan to make comparisons among different stages of prostate cancer in a larger patient sample.