Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients.
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.
Andrade
Valéria C C
VC
Discipline of Hematology and Hemotherapy, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil.
Vettore
André L
AL
Felix
Roberta S
RS
Almeida
Manuella S S
MS
Carvalho
Fabrício
F
Oliveira
José Salvador R
JS
Chauffaille
Maria Lourdes Lopes Ferrari
ML
Andriolo
Adagmar
A
Caballero
Otavia L
OL
Zago
Marco Antonio
MA
Colleoni
Gisele W B
GW
D000951:Antigens, Neoplasm / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C473332:CT7 antigen, human; C104948:CTAG1B protein, human; C510162:CTAG2 protein, human; C072013:MAGEA3 protein, human; C095203:MAGEA6 protein, human; C110905:MAGEC1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins