Background: The level of heat shock protein 60 (Hsp60) is elevated in tumor cells compared with normal prostate epithelium. Hsp60 is involved in tumor growth, invasion, and metastasis and is considered as a biomarker for cancer diagnosis and prognosis. Aim: To study the level of antibodies against prokaryotic homolog of human Hsp60 (GroEL) in prostate cancer (PCa) patients as an additional risk marker for the prediction of biochemical recurrence after radical prostatectomy (RP). Patients and Methods: A total of 55 patients with localized and locally advanced PCa, who had undergone RP between July 2013 and May 2014 were enrolled. Level of antibodies to GroEL and human Hsp60 was determined by enzyme-linked immunosorbent assay before surgery. Serum samples of blood donors with low reactivity to GroEL and human Hsp60 were used as controls. The relationship between IgG antibodies against bacterial Hsp60 and human Hsp60 and clinicopathological features were analyzed. The biochemical recurrence (BCR) free survival rate was estimated by the Kaplan — Meier method. The univariate and multivariate Cox regression models were used to evaluate the risk factors of BCR-free survival rate. Results: There were significant differences in anti-GroEL IgG levels between control and PCa patients while no significant differences in anti-human Hsp60 IgG levels between control and PCa patients were detected. During the follow-up period, 40/55 (72.7%) patients developed BCR. The time from surgery to BCR was from 18 to 72 months. Elevated IgG antibodies against bacterial Hsp60 in patients who had undergone RP were associated with early occurrence of biochemical relapse and lower 5-year BCR-free survival rate respectively (p < 0.001). The multivariate analysis indicated that IgG to GroEL (hazard ratio = 2.465; 95% confidence interval: 1.311–4.634, p < 0.05) could be independent prognostic factor in the patients who had developed BCR. Conclusion: Elevated levels of IgG antibodies against GroEL before surgery can predict early occurrence of BCR after RP and can serve as an additional independent risk biomarker of a BCR after RP.
Introduction. Prostate cancer antigen-3 (PCA3) is a genetic biomarker, which got widespread and demonstrated high diagnostic potential. This gene expresses only in prostate gland tissue, furthermore, malignant prostate neoplastic transformation leads to 70 – 100 time overexpression of it. Polyadenylated matrix RNA (mRNA) is a functional product of this gene, which do not translating into protein. Gene contains of four introns and three exon. Product of PCA’s gene detecting in post massage urine using polymerase chain reaction (PCR) in combination with reverse transcription. It could use as prognostic biomarker in patients with first negative biopsy or before it performing. Moreover, index of PCA3 can be useful in detecting tumor aggressiveness and decisions about further treatment options. Taking into account these facts, patients with high initial PSA level can avoid unnecessary biopsies. Objective: to determine critical cut-off value of PCA3 index as prognostic biomarker of PCa development. Materials and methods. Research based on routine and special test’s data of 243 men in Institute of Urology, National Academy of Medical Sciences of Ukraine in period of 2015–2020 year. RNA extraction from postmassage urine samples performed using RNeasy (Qiagen) kit. Statistical analysis performed using SPSS Statistics 19.0 (IBM SPSS Statistics 19.0) та SAS 12.0 (IBM Statistical Analysis System 12.0). Critical cut-off values determined using three methods: calculating of average value and (Xave) and standard deviation (SD) of it, Heiner index, and Youden’s index. Evaluation of optimality of determined critical cut-off values performed by comparative analysis using index of positive prognosis (IPP), index of negative prognosis (INP), diagnostic accuracy of method (DAM), Sp and Se for each of used methods. Results and discussion. First method demonstrated than 97,5 % of all results, which means absent of disease, was below critical cut-off values, due to statistical deviations and accurate demonstrate than in case of asymmetry or multimodal distribution this method was unsatisfied. Wherein IPP was 95 %, INP – 72 %, DAM – 78 %, Sp – 97,5 % and Se – 52 %. Calculation of PCA3 index area under ROC-curve was 0,810 (0,771–0,849). Using Heiner’s method critical cut-off value of PCA3 index was 14,0 с. u., where in IPP was 75 %, INP – 82 %, DAM – 78 %, Sp – 78 % and Se – 78 %. Critical cut-off values of PCA3 index 33,4 c. u. which calculated by Youden’s index demonstrated IPP – 98 %, INP – 73 %, DAM – 80 %, Sp – 99 % and Se – 57 %. Conclusions. The most optimal critical cut-off value for PCA3 index was determined using Youden’s index and was 33,4 c. u. Keywords: prostate cancer, PCA , prostate cancer antigen-3, PCA3, prostate cancer antigen-3 index, PCA3 index, critical cut-off values of PCA3 index.
Background: Prostate cancer (PCa) is the second most frequently diagnosed cancer in males worldwide and placed fifth in cancer mortality among males. Between 14–24% of PCa patients have newly diagnosed advanced stages, which paradoxically has remained stable over time. Aim: To estimate and compare long-term radical prostatectomy (RP) oncologic outcomes in patients with clinically locally advanced prostate cancer (LAPCa), to determine the prognostic significance of common clinical-pathological parameters. Patients and Methods: The study included 105 patients with LAPCa who underwent RP with extended pelvic lymphadenectomy between September 2003 — April 2015. Kaplan — Meier method was used for calculating biochemical recurrence- (BRFS), progression-free- (PFS), overall (OS), and prostate cancer-specific survival (PCSS) rates. Analyses of features associated with outcomes were conducted using Cox proportional hazards regression model. Results: Patients from cT3b group had worse PFS, OS and PCSS rates in comparison with cT3a, while there was no significant difference in BRFS rates. Preoperative serum prostate-specific antigen level (hazard ratio (HR) 1.023, 95% confidence interval (CI): 1.014–1.033, p < 0.001), pT3a (HR 3,027, 95% CI: 1.449–7.096, p < 0.01), pT3b (HR 2.792, 95% CI: 1.133–6.881, p < 0.05) pT4 stage (HR 31.12, 95% CI: 7.646–126.6 p < 0.001) and positive lymph nodes status (HR 6.503, 95% CI: 3.190–13.25, p < 0.001) were significant factors in BRFS. Preoperative serum prostate-specific antigen level (HR 1.018, 95% CI: 1.007–1.030, p = 0.001) and positive lymph nodes status (HR 3.191, 95% CI: 1.672–6.088, p < 0.001) were significant factors in PFS and PCSS. Conclusions: RP as the initial treatment option of multimodal therapy in the management of LAPCa patients demonstrates encouraging oncologic outcomes. Patients from the cT3b group had the worse rates of PFS, OS, and PCSS in comparison with the cT3a group. Heterogeneity of LAPCa patients’ outcomes reflects the insufficiency of the existing clinical risk classification for the prediction of systemic progression and cancer-specific survival.
Prostate cancer (PC) – refers to important and serious problems in urology. In Ukraine, PC ranks fourth in the structure of malignant neoplasms and third in the structure of mortality of men over 60 years. An important issue in the systemic approach to improving the quality of health care to ensure life expectancy while maintaining activity in men is not only the search for new highly sensitive, specific and non-invasive diagnostic methods that will detect PC in the early stages of the disease, but also the need to review and justify new threshold values of already known biomarkers, and the ability to find their optimal combinations. Many studies have shown that the detection of sarcosine by high performance liquid chromatography in combination with electrochemical analysis of the element has made it possible to prove the limit of detection of sarcosine in the urine of cancer patients. Imperfect study and limited use in clinical practice of prognostic features of acid phosphatase (PCP), citrate, zinc, sarcosine, spermine and myoinositol as biomarkers in post-massage urine prompted this kind of study. The objective: to evaluate the activity of acid phosphatase, citrate, zinc, sarcosin, spermine and monoinositol in postmassage urine as biomarkers of prostate cancer. Materials and methods. During the period 2016–2020, 246 men, aged 45 to 84, were examined on the basis of the Institute of Urology of the National Academy of Medical Sciences of Ukraine with complaints of urination disorders who were hospitalized or underwent a comprehensive examination. All patients received written consent to participate in the study, which was approved by the Ethics ComMission in the Institute of Urology of the National Academy of Medical Sciences of Ukraine. All PC patients underwent 12-point prostate biopsy under TRUS control using a G18 biopsy needle. During pathomorphological examination PC was classified according to Gleason’s score. Patients were divided as follows: with verified PC (1st group), patients with benign prostatic hyperplasia (BPH) (2nd group) and relatively healthy (3rd group). The content of PC biomarkers in post-massage urine was determined by known methods. Thus, acid phosphatase (EC 3.1.3.2) was analyzed by reaction with 1 mM para-nitrophenyl phosphate in 0.1 M flow buffer, pH 6.2; determination of citrate – ultraviolet; sarcosine – enzyme-linked colorimetric study and spermine – measurement of the amount of quinone-imine dye based on the formation of hydrogen peroxide; spermidine – by accumulation of l-pyrroline. All these methods were performed on a spectrophotometer «Specoll-211» (Germany). Zinc was determined by atomic absorption spectroscopy on an Analytik Jena ContrAA 300 spectrophotometer (Germany). Myoinositol was evaluated by the enzymatic cyclic method and measured by increasing the optical density of thio-NADH at 405 nm with an incubation of 37 °C. Results. Among the 246 patients studied after the examination, 107 (43.5%) had verified PC, 62 (58.0%) of which had a non-aggressive and 45 (42.0%) had aggressive form; 71 (28.9%) were diagnosed with BPH and 68 (27.6%) were found to be relatively healthy and included in the reference group. PAP data indicate that in almost healthy values of the indicator was the highest compared to those found in patients with BPH and PC, the lowest values were found in cases of PC, when its median was 1.5 IU/l. There is no evidence of a difference between the levels of PAP activity in patients with PC in the clinical stage T1-T2 and stages T3b. The use of PAP for the differential diagnosis of indolent and aggressive malignancies has not shown clinically significant results. In men without signs of prostate pathology, the concentration of citrate in post-massage urine, in contrast to patients with BPH, significant increased, and in patients with PC showed the opposite trend. Quantitative content of citrate in prostatic urine in the case of non-aggressive indolent tumors (Gleason index 5–6) significantly exceeded the value of the indicator in aggressive (Gleason 7–9 points) The concentration of zinc in prostatic urine in normal prostate and BPH almost did not differ. With increasing proliferation, especially under conditions of accelerated uncontrolled cell growth, apoptogenic function of zinc is first inhibited and then disappears at all, as a result of the comparison of zinc content in post-massage urine in patients with PC and in cases of pathology, its values, however, could not be established between patients with indolent and aggressive tumors. In terms of sarcosine content, patients without signs of prostate pathology and BPH did not differ statistically, while patients with PC in all parameters significantly exceeded the previous two groups. The median concentration of myoinositol in the functionally normal prostate was 35 mM, in patients with BPH there was a slight increase to 38 mM, and in PC the median value was 3 and 3.5 times smaller. In the absence of signs of prostate pathology, the concentration of spermine was 87 mM, in BPH the median increased to 114 mM, managed to identify significant differences. However, it was possible to trace the value of spermine content in determining the stage of the tumor process, namely between T1c – T2 and T3a. Conclusion. Enzymatic activity of acid phosphatase allows to detect PC but makes it impossible to make a differential diagnosis of the nature of the cancer process. The level of zinc in post massage urine did not show significant prognostic and differential diagnostic potential. Changes in the content of citrate, sarcosine and spermine in prostatic urine allow us to clearly predict not only the presence of PC, but also to make a differential diagnosis of cancer. Monoinositol showed only differential diagnostic potential in PC.
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