title: SSX cancer testis antigens are expressed in most multiple myeloma patients: co-expression of SSX1, 2, 4, and 5 correlates with adverse prognosis and high frequencies of SSX-positive PCs.
abstract: Cancer testis antigens (CTAs) are tumor-specific antigens that may be useful targets for cancer vaccines. Here, CTA expression was examined in multiple myeloma (MM), a B-cell cancer characterized by malignant plasma cells (PCs) in the bone marrow (BM), and monoclonal gammopathy of undetermined significance (MGUS), a condition that can progress to MM. We screened a panel of patient BMs at different stages of malignancy for CTA expression by reverse transcription polymerase chain reaction RT-PCR. Here, SSX (synovial sarcoma, X chromosome) emerged as a promising candidate for an MM vaccine, having a profile similar to currently studied CTA, NY-ESO-1, and MAGE. SSX1, 2, 4, and 5 expression was studied further in 114 MM (total SSX, 61% of patients; SSX1, 42%; SSX2, 23%; SSX4, 38%; SSX5, 35%), 45 MGUS (total SSX, 24% of patients; SSX1, 9%; SSX4, 20%), and 12 control (0/12, 0%) subjects. Several expression patterns were observed, the most predominant being co-expression of SSX1, 2, 4, and 5 (called group A expression, in 20% of MM), which correlated with reduced survival (P=0.0006). Of the four genes, SSX2 had the strongest association with reduced survival (P=0.0001). SSX protein expression ranged from 13.5% of PCs in an SSX1/SSX4 co-expressor to as high as 88% of PCs in group A expressor, exceeding reported frequencies of NY-ESO-1 and MAGE in MM. In single PCs from group A patients, we detected variable degrees of SSX co-expression, emphasizing the heterogeneity of CTA expression within tumor cell populations. These results demonstrate that SSX is a frequently expressed CTA in MM and highlight its potential as an MM vaccine candidate.
authors.affiliation: Department of Oncology, Cross Cancer Institute, and Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Taylor
authors.forename: Tony
authors.initials: T
authors.lastname: Reiman
authors.forename: Julie A
authors.initials: JA
authors.lastname: Pittman
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Keats
authors.forename: Diederik R H
authors.initials: DR
authors.lastname: de Bruijn
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mant
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Belch
authors.forename: Linda M
authors.initials: LM
authors.lastname: Pilarski
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D019496:Cancer Vaccines; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D010265:Paraproteinemias / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013737:Testis / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins