Prognostic Impact of Cancer Testis Antigens Expression in Advanced Stage Multiple Myeloma Patients.

Abstract

Background: Cancer testis antigens have become the most extensively studied antigen group in the field of tumor immunology. Aims: This study aims to analyze global expression of 14 CT (cancer/testis) antigens in MM to identify possible prognostic markers and therapeutic targets. Patients and Methods: The expression of MAGEA1, MAGEA2, MAGEA3/6, MAGEA4, MAGEA10, MAGEA12, BAGE1, MAGEC1/CT7, GAGE family, LAGE-1, PRAME, NY-ESO-1, SPA17 and SSX1 was studied by RT-PCR in: 15 normal tissues, one pool of 10 normal bone marrow samples, three normal tonsils and bone marrow aspirates from six normal donors, three monoclonal gammophaties of undetermined significance (MGUS), five solitary plasmacytomas, 39 MM samples (95% advanced stage) and MM cell line U266. CodeLink Human UniSet I Bioarrays 10,000 genes was used for arrays analyses. Results: SPA17 was positive in all normal tissues and was excluded for further analyses. MAGEC1/CT7 was positive in bone marrow aspirates from one MGUS and in one plasmacytoma. U266 cell line was positive for all CT antigens, except SSX1. The frequencies of CT antigens expression in MM patients were: MAGEC1/CT7 = 30/39 (77%); LAGE-1 = 19/39 (49%); MAGEA3/6 = 16/39 (41%); MAGEA2 = 14/39 (36%); GAGE family = 13/39 (33%); NY-ESO-1 = 13/39 (33%); BAGE-1 = 12/39 (28%); MAGEA1 = 10/39 (26%); PRAME = 9/39 (23%); SSX-1 = 10/39 (26%); MAGEA12 = 8/39 (20.5%); MAGEA4 and MAGEA10 = 0%. Cox’s regression model showed that GAGE family positivity and number of positive CT antigens > 6 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. Three samples predominantly positive (> 6) and three samples predominantly negative (0 or 1) for the 13 analyzed CT antigens were submitted to microarrays analyses. 147 genes were overexpressed in predominantly positive CT antigens samples. Conclusions: Based on our findings, MAGEC1/CT7, MAGEA3/6 and LAGE-1 seem good candidates for immunotherapy, since together they are overexpressed in 85% of our MM cases. Besides, GAGE family expression, number of CT antigens > 6 and MAGEC1/CT7 seem to have impact on MM prognosis. Also, the results of arrays analyses corroborate the hypothesis that MM can be separate in two groups: predominantly positive and predominantly negative for CT antigens, meaning that these antigens may have important role for MM biology.

Pattern and clinical significance of cancer‐testis gene expression in head and neck squamous cell carcinoma

“…8,11 While PRAME expression has been reported as a predictor of both poorer and better patient outcome (e.g. in breast cancer and promyelocytic leukemia, respectively), 34,45,46 it had no influence on survival in our cohort of HNSCC patients. We are the first to report the extent of HERV-K-MEL expression in a large series of HNSCC tumors.…”

“…32 Caution however must be applied in interpreting positive 57B staining as MAGE-A4 positivity, as the antibody can also recognize other MAGE-A proteins. 17,18 Expression of other CT genes has also been generally associated with poor prognosis, 24,33,34 with only few studies revealing a positive effect. 27,35 None of the CT genes tested in this study was associated with better survival.…”

Expression of MAGE‐A and NY‐ESO‐1 cancer/testis antigens is enriched in triple‐negative invasive breast cancers

“…Cancer/testis antigens (CTAs) belong to a group of proteins that are expressed in the developing embryo, are restricted to the testis in the adult, and are aberrantly re-expressed in malignancy, particularly high-grade and advanced-stage tumours, including TNBC. [23][24][25][26][27][28] Members of the melanomaassociated antigen (MAGE) family and New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) are among the CTAs being actively investigated as cancer immunotherapy targets. They have been shown to evoke spontaneous cytotoxic T-cell responses in melanoma, oesophageal carcinoma, bladder cancer, and non-small-cell lung carcinoma.…”

Standardisation of minimal residual disease in multiple myeloma

“…A pilot study published in 2016 by South African scientists investigated the possibility of detecting CMCs by their expression of cancer testis antigen MAGE C1 in peripheral blood. The expression of MAGE C1 had been found in the 85%-100% of BM PCs of patients with symptomatic MM (Andrade et al, 2008;Tinguely et al, 2008), but its presence was demonstrated in PB on early stem cell immature B lymphocyte of all patients with symptomatic MM, as well as in the clonal PCs compartment (Shires, Teuchert, Wienand, Shankland, & Novitzky, 2016;Wienand & Shires, 2015). Using MFC (CD34/CD19/ CD45/MAGE C1, and CD138/CD45/MAGE C1) and qRT-PCR techniques (primers and probes for the amplification of MAGE C1), they suggested a valuable tool to routinely monitor clonal malignant progenitor cells destined to feed the progression of the disease.…”