Serum Thymidine Kinase 1 - Potential Prostate Cancer Biomarker: A Clinical Study.

BACKGROUND/AIM: Serum thymidine kinase 1 (STK1) is a proliferation biomarker that has been used as a diagnostic marker of several malignant diseases. However, there are limited data for prostate cancer (PCa). PATIENTS AND METHODS: In this study, we retrospectively analysed serum samples from 169 patients with biopsy confirmed PCa, who had been indicated for radical prostatectomy (RP) between 2013-2016. The results were compared with those in serum samples from 39 healthy men. We used commercially available enzymatic immunoassay to determine the levels of STK1. The patients were divided into groups according to the Gleason score (GS) and risk factors for adjuvant radiotherapy (aRT), which were defined as GS 8-10, pT3, and a positive surgical margin. RESULTS: The median serum level of STK1 in PCa patients was 0.289 pmol/l. In the control group, the median value was 0.0116 pmol/l (p<0.001). By comparing the patients with GS≤6 vs. 7 vs. ≥8 (p=0.01), we found statistically significant differences. In the correlation of STK1 values with risk factors, we found statistically significant differences both in comparison of 0 vs. 1 vs. 2 vs. 3 risk factors (p=0.021), as well as ≤1 vs. 2≥ risk factors (p=0.009). CONCLUSION: The levels of STK1 are significantly higher in patients with PCa than those in healthy controls. Furthermore, STK1 values correlate with GS and predefined risk factors for aRT. Therefore, STK1 can be considered as a potential tumour marker of PCa diagnosis and risk stratification.

HNF1B, EZH2 and ECI2 in prostate carcinoma. Molecular, immunohistochemical and clinico-pathological study.

Hepatocyte nuclear factor 1 beta (HNF1B) is a tissue specific transcription factor, which seems to play an important role in the carcinogenesis of several tumors. In our study we focused on analyzing HNF1B in prostate carcinoma (PC) and adenomyomatous hyperplasia (AH), as well as its possible relation to the upstream gene EZH2 and downstream gene ECI2. The results of our study showed that on an immunohistochemical level, the expression of HNF1B was low in PC, did not differ between PC and AH, and did not correlate with any clinical outcomes. In PC, mutations of HNF1B gene were rare, but the methylation of its promotor was a common finding and was positively correlated with Gleason score and stage. The relationship between HNF1B and EZH2/ECI2 was equivocal, but EZH2 and ECI2 were positively correlated on both mRNA and protein level. The expression of EZH2 was associated with poor prognosis. ECI2 did not correlate with any clinical outcomes. Our results support the oncosuppressive role of HNF1B in PC, which may be silenced by promotor methylation and other mechanisms, but not by gene mutation. The high expression of EZH2 (especially) and ECI2 in PC seems to be a potential therapeutic target.

Diagnostic benefits of mindin as a prostate cancer biomarker: Dijagnosticke prednosti mindina kao biomarkera raka prostate.

BACKGROUND: It has been shown that decreased expression and activity of extracellular matrix protein mindin correlate with various types of cancers including breast, colon and lung cancers. The aim of the presented study was to investigate the serum mindin levels in prostate cancer. METHODS: Mindin concentrations in serum were measured in 56 patients with prostate cancer (mean age 68 years) and in control group of 29 healthy men (mean age 64 years) using commercially available enzymatic immunoassay (Cusabio, WuHan, China). The patients were divided with respect to the severity of the disease into two groups according to the EAU guidelines (stage 1, 2 - less severe tumours, stage 3, 4 - severe tumours). RESULTS: Serum mindin concentrations were significantly elevated in the group of healthy individuals unlike in the patients with prostate cancer (2.12 ng/mL vs 0.78 ng/mL, with P=0.0007, AUC=0.705). Patients with less severe tumours (stage 1, 2) and severe tumours (stage 3, 4) had significantly decreased levels of S-mindin as well (P=0.0037), although the difference in serum mindin concentrations between the patients with less severe and severe tumours was not significant. CONCLUSIONS: Concentrations of mindin were decreased in patients with prostate cancer and reduced in patients with less severe prostate cancer as well. Mindin appears to be a promising diagnostic marker useful in the diagnosis of prostate cancer.

Thymidine Kinase-1 as Additional Diagnostic Marker of Prostate Cancer.

BACKGROUND: Thymidine kinase-1 (TK-1) is associated with proliferation and malignancy and has been extensively studied as a diagnostic biomarker for a variety of tumors, but there are limited data for prostate cancer. METHODS: TK-1 concentrations in serum were measured in 59 patients with prostate cancer (mean age 68 years) and in the control group of 28 healthy men (mean age 63 years) using commercially available enzymatic immunoassay (LSBio, Inc., Seattle, WA, USA). The patients were divided with respect to the severity of the disease into two groups according to the European Association of Urology (EAU) guidelines (Stage 1, 2 - less severe tumors, stage 3 - severe tumors). RESULTS: Serum thymidine kinase-1 concentrations were significantly elevated in the group of the patients with prostate cancer compared to the healthy individuals (0.204 pmol/L vs. 0.072 pmol/L, with p < 0.0001). Diagnostic efficiency of serum TK-1 concentrations was 0.792 with the specificity of 53.6% and sensitivity of 94.9%. Patients with less severe tumors (Stage 1, 2) and severe tumors (Stage 3) had significantly increased levels of TK-1 as well (p < 0.0001). Combination of TK-1 and PSA investigation in patients with PCa improve the diagnostic validity of TK-1 (AUC = 0.87). CONCLUSIONS: Concentrations of thymidine kinase 1 are increased in all patients with prostate cancer and even more in patients with severe prostate cancer. Thymidine kinase 1 appears to be a promising additional diagnostic marker promising in patients with prostate cancer.