The main advantage of urinary biomarkers is their noninvasive character and the ability to detect multifocal prostate cancer (CaP). We have previously implemented a quadruplex assay of urinary markers into clinical practice (PCA3, AMACR, TRPM8 and MSMB with KLK3 normalization). In this study, we aimed to validate it in a larger cohort with serum PSA 2.5-10 ng/mL and test other selected transcripts and clinical parameters, including the percentage of free prostate-specific antigen (PSA) (% free PSA) and inflammation. In the main cohort of 299 men, we tested the quadruplex transcripts. In a subset of 146 men, we analyzed additional transcripts (CD45, EPCAM, EZH2, Ki67, PA2G4, PSGR, RHOA and TBP). After a prostate massage, the urine was collected, RNA isolated from a cell sediment and qRT-PCR performed. Ct values of KLK3 (i.e., PSA) were strongly correlated with Ct values of other genes which play a role in CaP (i.e., PCA3, AMACR, TRPM8, MSMB and PSGR). AMACR, PCA3, TRPM8 and EZH2 mRNA expression, as well as % free PSA, were significantly different for BPH and CaP. The best combined model (% free PSA plus PCA3 and AMACR) achieved an AUC of 0.728 in the main cohort. In the subset of patients, the best AUC 0.753 was achieved for the combination of PCA3, % free PSA, EPCAM and PSGR. PCA3 mRNA was increased in patients with inflammation, however, this did not affect the stratification of patients indicated for prostate biopsy. In conclusion, the percentage of free PSA and urinary markers contribute to a more accurate indication for prostate biopsy.
- MeSH
- analýza moči metody MeSH
- biopsie MeSH
- časná detekce nádoru metody MeSH
- hyperplazie prostaty MeSH
- lidé MeSH
- nádorové biomarkery * moč MeSH
- nádory prostaty * diagnóza MeSH
- prostatický specifický antigen moč MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: PTEN is a tumour suppressor protein with phosphatase activity frequently altered in several types of human cancers. MATERIALS AND METHODS: The PTEN effect was studied on the cell cycle (by bromdeoxyuridine incorporation) and on the phosphatidylinositol-3-kinase/protein kinase B/Akt (PI3-K/PKB/Akt) pathway regulating proteins (by immunocytochemical, Western blot analysis and kinase assay) upon transfection of wild-type PTEN and its mutant H123Y in breast cancer cell lines. RESULTS: The expression of the important proteins in the MCF-7 and BT-549 cells was characterised and the cellular localisation of PTEN was analysed. Transfection of H123Y led to the down-regulation of p27(Kip1) and p21(Waf1/Cip1) protein levels and the up-regulation of phosphorylated PKB/Akt. An overexpression of PTEN decreased cyclin E/cdk2 activity and inhibited S-phase entry in MCF-7. In BT-549 these changes were not observed, but overexpression of PTEN led to a diminution of PKB/Akt phosphorylation. CONCLUSION: PTEN function is mediated through the inhibition of the cell cycle and PKB/Akt phosphorylation in breast cancer cells.
- MeSH
- buněčný cyklus fyziologie MeSH
- cyklin-dependentní kinasa 2 metabolismus MeSH
- cykliny biosyntéza MeSH
- financování organizované MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- fosfohydroláza PTEN biosyntéza genetika metabolismus MeSH
- fosforylace MeSH
- inhibitor p21 cyklin-dependentní kinasy biosyntéza MeSH
- intracelulární signální peptidy a proteiny MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prsu enzymologie genetika metabolismus patologie MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- S fáze genetika MeSH
- transfekce MeSH
- Check Tag
- lidé MeSH
- MeSH
- apoptóza MeSH
- finanční podpora výzkumu jako téma MeSH
- karcinom diagnóza růst a vývoj MeSH
- lidé MeSH
- nádorový supresorový protein p53 MeSH
- nádory prostaty komplikace terapie MeSH
- prognóza MeSH
- protoonkogenní proteiny c-bcl-2 MeSH
- regulace genové exprese u nádorů MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
