Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Abstract

Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1–8, and MAGE-C2, a combination of at least three CT genes—desirable for circumventing tumor escape mechanisms—is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

“…CTA expression in myeloma has been evaluated in large patient sets but emphasis has so far been on newly diagnosed patients. 13,16,29,30 Compared to the study of Condomines et al, 16 presence of gene expression frequency differed no more than 2-fold in 73% of overlapping genes when compared to the frequencies found in newly diagnosed patients in our study. Of these, 12 are highly correlated with a difference in frequency of no more than 1.5-fold, including MAGEC1, MAGEA5 and SSX3; 61%, 26% and 3% in our study and 66%, 22% and 3% in the study of Condomines et al 16 In some cases, different probe sets belonging to the same gene may explain the difference in expression frequencies between the two studies.…”

“…However, as indicated below, our results corresponded well to a previous report on CTA expression as determined using Affymetrix GeneChips in newly diagnosed cases only. 16 The difference between studies may be attributed to differences in the techniques used. CTA expression in myeloma has been evaluated in large patient sets but emphasis has so far been on newly diagnosed patients.…”

“…presence of CTA expression has been linked to shorter survival. 16 Similarly, in other tumor types, CTA expression has been linked to prognosis. 17,18 Prognostic implications of CTAs post therapy have not been systematically evaluated.…”

Systematic identification of cancer-specific MHC-binding peptides with RAVEN

“…Among them we found not only many established CSGs such as LIPI for Ewing sarcoma, 21 PRAME for neuroblastoma 22,23 and members of the MAGE -family for germinoma, 24 neuroblastoma, 25 synovial sarcoma, 26 multiple myeloma, 27 diffuse large B cell lymphoma (DLBCL), 28 and osteosarcoma, 29 but also many novel candidates of which some appear to be suitable for targeting multiple cancer entities (Figure 2, Supplementary Table 5, Supplementary Figure 1).

10.1080/2162402X.2018.1481558-F0002Figure 2.Overexpressed CSGs in multiple cancer entities identified with RAVEN.

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L’intrusion des régulateurs de l’épigénome mâle dans les cellules somatiques cancéreuses

“…Enfin, un certain nombre d'antigènes C/T ont été identifiés sur la base de leur profil d'expression [35,36]. L'expression anormale d'un ou plusieurs C/T est détectée dans de nombreux cancers somatiques, tumeurs solides [37][38][39][40] ou hémopathies [41,42]. Cela peut être exploité pour le développement de marqueurs indiquant la présence et/ou de l'évolution d'un processus tumoral, basés sur la détection des transcrits correspondants [37], ou des protéines, ou même d'anticorps circulants dirigés contre ces C/T [43].…”