Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jun 26;107(1):116-22.
doi: 10.1038/bjc.2012.215. Epub 2012 May 17.

Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma

L Dyrskjøt  1 , K Zieger, T Kissow Lildal, T Reinert, O Gruselle, T Coche, M Borre, T F Ørntoft
Affiliations

Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma

L Dyrskjøt et al. Br J Cancer. .

Abstract

Background: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out.

Methods: We used specific q-RT-PCR assays to analyse the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information.

Results: Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed PRAME. In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was significantly associated with a shorter progression-free survival. In addition, we found that patients with tumours expressing PRAME responded poorly to chemotherapy (P=0.02, χ(2)-test).

Conclusion: Cancer-testis genes are frequently expressed in bladder cancer and especially in tumours of high stage and grade. In addition, the CT gene expression may have both prognostic and predictive value. Development of specific immunotherapy against the CT antigens in bladder cancer may ultimately increase patient survival.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Expression of CT genes and correlation to outcome. Comparison of CT gene expression for all tumours combined (A) and stratified for stage (B) and grade (C). Expression is plotted as: −1x(cross threshold (Ct) CT gene – Ct beta actin). High Ct values indicate high gene expression and vice versa. The colour coding in (B and C) is the same as in A. Kaplan–Meier survival estimates of progression-free survival as a function of MAGE-A3 expression (D), NY-ESO-1 expression (E), LAGE-1 expression (F) and PRAME expression (G). Only patients with non-muscle-invasive tumours and no prior muscle-invasive tumours were included in the analysis (n=124).
Figure 2
Figure 2
Methylation status of MAGE-A3, PRAME, LAGE-1 and NY-ESO-1 promoter regions. Distribution plots of methylation index (beta values) differences between normal samples and tumours. Beta values range from 0 to 1, where 0 indicates no methylation and 1 indicates full methylation. Statistical differences were calculated using the Mann–Whitney test.
See this image and copyright information in PMC

References

    1. Avritscher EB, Cooksley CD, Grossman HB, Sabichi AL, Hamblin L, Dinney CP, Elting LS (2006) Clinical model of lifetime cost of treating bladder cancer and associated complications. Urology 68(3): 549–553 - PubMed
    1. Bergeron A, Picard V, LaRue H, Harel F, Hovington H, Lacombe L, Fradet Y (2009) High frequency of MAGE-A4 and MAGE-A9 expression in high-risk bladder cancer. Int J Cancer 125(6): 1365–1371 - PubMed
    1. Caballero OL, Chen YT (2009) Cancer/testis (CT) antigens: potential targets for immunotherapy. Cancer Sci 100(11): 2014–2021 - PMC - PubMed
    1. De Carvalho DD, Binato R, Pereira WO, Leroy JM, Colassanti MD, Proto-Siqueira R, Bueno-Da-Silva AE, Zago MA, Zanichelli MA, Abdelhay E, Castro FA, Jacysyn JF, Amarante-Mendes GP (2011) BCR-ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients. Oncogene 30(2): 223–233 - PubMed
    1. Epping MT, Hart AA, Glas AM, Krijgsman O, Bernards R (2008) PRAME expression and clinical outcome of breast cancer. Br J Cancer 99(3): 398–403 - PMC - PubMed

Publication types