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. 2008 Feb 1:8:2.

Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients

Valéria C C Andrade  1 , André L Vettore, Roberta S Felix, Manuella S S Almeida, Fabrício Carvalho, José Salvador R Oliveira, Maria Lourdes Lopes Ferrari Chauffaille, Adagmar Andriolo, Otavia L Caballero, Marco Antonio Zago, Gisele W B Colleoni
Affiliations

Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients

Valéria C C Andrade et al. Cancer Immun. .

Abstract

This study aims to analyze the expression of 14 cancer/testis (CT) antigens in multiple myeloma (MM) to identify possible prognostic markers and therapeutic targets. The expression of MAGEA1, MAGEA2, MAGEA3/6, MAGEA4, MAGEA10, MAGEA12, BAGE1, MAGEC1/CT7, the GAGE family, LAGE-1, PRAME, NY-ESO-1, SPA17 and SSX1 was studied by RT-PCR in 15 normal tissues, a pool of 10 normal bone marrow samples, 3 normal tonsils and bone marrow aspirates from 6 normal donors, 3 monoclonal gammopathies of undetermined significance (MGUS), 5 solitary plasmacytomas, 39 MM samples (95% advanced stage) and the MM cell line U266. MAGEC1/CT7 was expressed in bone marrow aspirates from one MGUS and one plasmacytoma. The frequencies at which CT antigen were found to be expressed in MM patients were MAGEC1/CT7 77%, LAGE-1 49%, MAGEA3/6 41%, MAGEA2 36%, GAGE family 33%, NY-ESO-1 33%, BAGE-1 28%, MAGEA1 26%, PRAME 23%, SSX-1 26%, MAGEA12 20.5%, MAGEA4 0%, and MAGEA10 0%. Cox's regression model showed that GAGE family expression and having >6 CT antigens expressed were independent prognostic factors when all patients were analyzed. However, MAGEC1/CT7 expression was the only independent prognostic factor when non-transplanted patients where analyzed. Based on our findings, MAGEC1/CT7, MAGEA3/6 and LAGE-1 are good candidates for immunotherapy, since together they cover 85% of our MM cases. Furthermore, expression of the GAGE family, >6 CT antigens and MAGEC1/CT7 seem to have impact on MM prognosis.

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Figures

Table 1
Table 1
Primer sequences, references and RT-PCR conditions used in this study.
Figure 1
Figure 1
Table 2
Table 2
Baseline characteristics of patients with MGUS, plasmacytoma and multiple myeloma.
Table 3
Table 3
CT antigen expression in normal tissues.
Figure 2
Figure 2
Table 4
Table 4
Variables identified as independent prognostic factors in all patients, and in non-transplanted patients only, by Cox's regression model.
Table 5
Table 5
MAGE-C1/CT7, GAGE family and CT antigen expression in the 8 transplanted MM patients.
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