- Publikační typ
- abstrakt z konference MeSH
Current diagnostic techniques are inefficient in distinguishing latent and low-risk forms of prostate cancer from high-risk forms. The present study is focused on determination of putative tumor markers of aggressive high-grade forms of prostate cancer. Potential markers were determined in blood sera of 133 patients (82 cases and 51 controls) and in cell lines (Gleason score 9-derived 22Rv1 and normal tissue derived PNT1A) on mRNA and protein levels. Alpha-methylacyl-CoA racemase (AMACR), metallothionein classes 1A and 2A (MT1A and MT2A) were determined and compared to prostate specific antigen (PSA) levels. On mRNA level, significantly increased expression of MT2A (2.4-fold), PSA (2.6-fold) and AMACR (8.4-fold) and insignificantly (1.9-fold) elevated MT1A in 22Rv1 compared to non-tumor PNT1A were determined. On protein level, significant enhancement of free PSA and total PSA in tumor cell line was evident. AMACR protein was 1.5-fold elevated in tumor line (below the level of significance). Contrary to mRNA, significantly (p = 0.01) reduced level of MT protein in tumor lines was determined. In the case of serum level, significantly enhanced MT level (4.5-fold) in patients' sera was found. No significant changes were observed in the case of AMACR. These findings indicate possible alternative role of MT to PSA prostate cancer marker. In addition, level of AMACR is distinctly higher in the Gleason score 9 in serum of patients and MT shows a descending trend in relation to Gleason score.
- MeSH
- adenokarcinom genetika metabolismus patologie MeSH
- dospělí MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- metalothionein genetika metabolismus MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory prostaty genetika metabolismus patologie MeSH
- prognóza MeSH
- prostatický specifický antigen genetika metabolismus MeSH
- racemasy a epimerasy genetika metabolismus MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- stupeň nádoru MeSH
- western blotting MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Current diagnostic techniques of prostate cancer cannot efficiently distinguish the latent and low-risk forms from the high-risk significant forms of prostate cancer. Caveolin-1 (Cav-1), except other functions, plays an important role in cell transformation and the process of tumorigenesis. Furthermore, Cav-1 is involved in metastatic processes. It has also been shown that Cav-1 expression is induced under stress conditions, such as oxidative stress. The present study focused on the determination of prognostic markers of aggressive (high-grade) forms of prostate cancer. We determined serum Cav-1 and serum markers of antioxidant activity-glutathione (GSH), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant capacity (TEAC), ferric-reducing antioxidant power (FRAP), N,N-dimethyl-1,4-diaminobenzene (DMPD), free radicals method (FRK) and blue chromium peroxide (Cro) in 97 serum samples (82 prostate cancer patients and 15 controls). We found insignificant differences in Cav-1 between the sera of patients and controls (5.69 in the cancer group vs. 5.42 ng/ml in the control group). However, we found a significant (p<0.004) 2.8-fold elevation of Cav-1 in high tumour stages (TNM T4) compared to lower stages and a significant positive association with histological grading (r=0.29, p=0.028). We also found that in patients with high serum Cav-1 the antioxidant capacity of the body is reduced. These findings indicate that Cav-1 may be an interesting tool for the prediction of disease burden.
- MeSH
- antioxidancia metabolismus MeSH
- bifenylové sloučeniny krev MeSH
- chromany (dihydrobenzopyrany) krev metabolismus MeSH
- glutathion krev MeSH
- kaveolin 1 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory prostaty krev MeSH
- oxidační stres MeSH
- peroxidy krev MeSH
- pikráty krev MeSH
- senioři MeSH
- sloučeniny chromu krev MeSH
- volné radikály krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři 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
Současné možnosti diagnostiky karcinomu prostaty neumožňují odlišit agresivní (signifikantní tumory) od klinicky latentních (nesignifikantních forem). Práce se zaměřuje na stanovení hladiny klinicky využitelných tumorových markerů karcinomu prostaty: alfa-metyl CoA-racemáza (AMACR), caveolin-1, metalothionein (MT), p53, NF-?B, c-FOS, c-JUN, Ki-67, prostatický specifický antigen (PSA), ZIP1 a ZnT-1 na úrovni prostatické tkáně (reprezentované buněčnými liniemi 22Rv1 a PNT1A) a v séru pacientů s histologicky ověřeným adenokarcinomem (82 karcinomových a 51 kontrolních sér). Na úrovni mRNA bylo zjištěno snížení exprese Cav-1, NF-?B, c-FOS a c-JUN a zvýšení exprese metalothioneinu, AMACR, PSA, Ki-67, MMP-9 a zinkových transportérů ZIP1 a ZnT-1. V séru je popsáno signifikantní zvýšení metalothioneinu nad hladinu 1 µM. Hladina caveolinu-1 se významně zvyšuje u high-grade tumorů, což jej staví do pozice možného markeru agresivní formy karcinomu prostaty.
Current methods for diagnosis of prostate carcinoma do not enable us to distinguish aggressive tumours (significant tumours) from clinically latent tumours (non-significant tumours). This study aims to determine levels of potential clinically important tumour markers such as alpha-methyl CoA-racemase (AMACR), caveolin-1, metallothionein (MT), p53, NF-?B, c-FOS, c-JUN, Ki-67, prostate-specific antigen (PSA), ZIP1 and ZnT-1 in prostatic tissue represented by 22Rv1 (tumour) and PNT1A (healthy) cell lines and in blood serum of patients with histologically evaluated adenocarcinoma (82 tumour patients and 51 healthy volunteers). Based on mRNA expression, it was found that Cav-1, NF-?B, c-FOS and c-JUN were down-regulated and MT, AMACR, PSA, Ki-67, MMP-9 and zinc transporters ZIP1 and ZnT-1 were up-regulated. In serum, the level of MT was significantly enhanced above 1 µM. Caveolin-1 levels were significantly increased in high-grade tumours, which points to the possibility of using this protein as a marker for the aggressive form of prostate carcinoma.
- Klíčová slova
- nádorová onemocnění, imunodetekce, molekulárně-biologické techniky,
- MeSH
- 2D gelová elektroforéza využití MeSH
- diagnostické techniky molekulární metody MeSH
- elektrochemie metody MeSH
- financování organizované MeSH
- kaveolin 1 diagnostické užití MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádorové buněčné linie chemie MeSH
- nádory prostaty genetika krev MeSH
- polymerázová řetězová reakce využití MeSH
- prostatický specifický antigen izolace a purifikace krev MeSH
- senzitivita a specificita MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
