The melanoma-associated antigen-A3, -A4 genes: relation to the risk and clinicopathological parameters in breast cancer patients

Hussein, Yousri M.; Gharib, Amal F.; Etewa, Rasha L.; El‐Shal, Amal S.; Abdel-Ghany, Mohamed Esmat; Elsawy, Wael H.

doi:10.1007/s11010-011-0734-4

Cited by 13 publications

(9 citation statements)

References 33 publications

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“…Furthermore MAGE-A proteins may reduce malignant potential by inhibiting the tumor suppressor p53 (9, 24). Finally, MAGE is expressed in a variety of malignancies (25–27), opening the possibility of extending this immunotherapeutic strategy to other hematological malignancies and tumors.…”

Section: Discussionmentioning

confidence: 99%

Improving T-cell Therapy for Relapsed EBV-Negative Hodgkin Lymphoma by Targeting Upregulated MAGE-A4

Cruz

Gerdemann

Leen

et al. 2011

Clinical Cancer Research

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Rationale Patients with Hodgkin’s Lymphoma (HL) relapsing after hematopoietic stem cell transplant (HSCT) have limited options for long-term cure. We have shown that infused cytotoxic T cells (CTL) targeting Epstein Barr virus (EBV)-derived proteins induced complete remissions in EBV+ HL patients. A limitation of this approach is that up to 70% of relapsed HL tumors are EBV-negative. For these patients an alternative is to target the cancer/testis antigen MAGE-A4 present in EBV antigen-negative HL tumors. Furthermore, epigenetic modification by clinically available demethylating agents can enhance MAGE-A4 expression in previously MAGE-negative tumors. Experimental Design We explored the feasibility of combining adoptive T cell therapy with epigenetic modification of tumor antigen expression. We further characterized MAGE-A4-specific T cell phenotype and function, and examined the effects of the epigenetic-modifying drug decitabine on these T cells. Results Cytotoxic T cells were generated specifically recognizing MAGE-A4 expressed by autologous HL targets and tumor cell lines. Decitabine – previously shown to increase tumor antigen expression in Hodgkin’s Lymphoma – did not compromise MAGE-A4 specific T cell phenotype and function. In patients treated with decitabine, expanded MAGE-A4 specific T cells had a broader anti tumor T cell repertoire consistent with increased antigen stimulation in vivo. Conclusions Adoptive transfer of MAGE-A4 specific T cells, combined with epigenetic-modifying drugs to increase expression of the protein may improve treatment of relapsed Hodgkin’s Lymphoma.

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Section: Discussionmentioning

confidence: 99%

Improving T-cell Therapy for Relapsed EBV-Negative Hodgkin Lymphoma by Targeting Upregulated MAGE-A4

Cruz

Gerdemann

Leen

et al. 2011

Clinical Cancer Research

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“…Twenty-one cancer/testis antigens (8%) and 119 testis proteins (11 testis-specific proteins) were included in the breast cancer protein profiles and these proteins warrant further study. Among these proteins, a recent study showed that MAGE-A3 and A4 in the peripheral blood of breast cancer patients may have potential prognostic and predictive implications (44). All of these proteins are promising specific tumor markers of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Differential proteomic analysis of pathway biomarkers in human breast cancer by integrated bioinformatics

Liu¹,

Jin²,

Shen³

2012

Oncology Letters

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Abstract. The aim of this study was to better understand the altered functional modules in breast cancer at pathway and network levels. An integrated bioinformatics analysis of differentially expressed proteins in human breast cancer was performed. Breast cancer protein profiles were constructed by data mining proteins in literature and public databases, including 1031 proteins with 153 secretory and 69 cell surface proteins. An experimental investigation was performed by two-dimensional electrophoresis, and 4 proteins were further validated by western blotting. Enriched bioinformatics functions were clustered. This study may be used as a reference in further studies to help identify the underlying biological interactions associated with breast cancer and discover potential cancer targets. IntroductionBreast cancer is the most common neoplasia in women and its pathogenesis is related to an acquired or inherited genetic disorder influenced by environmental, behavioral or reproductive factors (1). Cancer biomarker discovery is important for both cancer biology and clinical applications. These markers may come from DNA, RNA, miRNA or proteins (2), with proteins being the most significant (3).The development and improvement of biotechnologies has allowed researchers to perform high-throughput analyses of genomes, transcriptomes and proteomes in health and disease, and identify hundreds of potential biomarkers (4), offering the potential to discover diagnostic, prognostic or therapeutic targets. However, less than two dozen cancer biomarkers are currently approved by the Food and Drug Administration (FDA) (5), including only 9 protein biomarkers identified in the blood (6). Due to the lack of sensitivity and specificity of these known biomarkers (7), researchers continue to search for more significant targets. Proteomics is a promising approach for the discovery of cancer targets and biomarkers (8). The mapping of proteome profiles and differential proteomics has been widely performed in breast cancer to identify potential biomarkers (9). The identified proteins were reported to have potential clinical significance, and certain proteins may be used as potential diagnostic, prognostic or predictive biomarkers (10,11,12,13,14). However, due to the heterogeneity in the different studies, including experimental design, sample collection and classification and analytical method (15), these results lack good reproducibility and require further validation before they can be used in clinical detection and to explain the underlying mechanisms of breast cancer. In addition, few protein candidates were warranted to be specific to breast cancer, and were often differentially expressed in other cancer types (16). Hence, research encountered the challenge of how to decipher and use these individual results and bring them into clinical applications. In addition, an understanding of the underlying biological mechanisms of carcinogenesis and the altered molecular events in breast cancer at integrated pathway levels is necessary. Prot...

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“…Ayyoub et al (16) reported that MAGEA3 and MAGEA6 expression in primary breast cancer is associated with hormone receptor-negative status, high histological grade and poor survival. Cabezón et al (17) indicated that MAGEA3 and MAGEA4 may be associated with risk and the clinicopathological parameters of breast cancer (17,18). In breast cancer, MAGEA9-A11 have been identified as being associated with poor prognosis (19–23).…”

Section: Introductionmentioning

confidence: 99%

Prognostic roles of MAGE family�members in breast cancer based on KM‑Plotter Data

Jia¹,

Zhao²,

Wang³

et al. 2019

Oncol Lett

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Breast cancer is the second leading cause of cancer-associated mortality among women worldwide, and the prevalence and mortality rates associated with this disease are high in Western countries. The melanoma-associated antigen (MAGE) family proteins are well-known tumor-specific antigens; this family includes >60 proteins that serve an important part in cell cycle withdrawal, neuronal differentiation and apoptosis. The aim of the present study was to identify a biomarker within the MAGE family that is specific for breast cancer. In the present study, the prognostic role of MAGE mRNA expression was investigated in patients with breast cancer using the Kaplan-Meier plotter database. The prognostic value of MAGE members in the different intrinsic subtypes of breast cancer was further investigated, as well as the clinicopathological features of the disease. The results of the present study indicated that patients with breast cancer that had high mRNA expression levels of MAGEA5, MAGEA8, MAGEB4 and MAGEB6 had an improved relapse-free survival, whereas those with high mRNA expression levels of MAGEB18 and MAGED4 did not. These results suggested that MAGEA5, MAGEA8, MAGEB4 and MAGEB6 may have roles as tumor suppressors in the occurrence and development of breast cancer, whereas MAGEB18 and MAGED4 may possess carcinogenic potential. MAGED2, MAGED3 and MAGEF1 had different effects depending on the type of breast cancer. In particular, high MAGEC3 mRNA expression was associated with worse RFS in lymph node-positive breast cancer, but with improved RFS in lymph node-negative breast cancer. In patients with wild-type TP53 and patients with different pathological grades of breast cancer, MAGEE2, MAGEH1 and MAGEL2 were more worthy of attention as potential prognostic factors. The results of the present study may help to elucidate the role of MAGE family members in the development of breast cancer, and may promote further research that identifies MAGE-targeting reagents for the treatment of breast cancer.

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The melanoma-associated antigen-A3, -A4 genes: relation to the risk and clinicopathological parameters in breast cancer patients

Cited by 13 publications

References 33 publications

Improving T-cell Therapy for Relapsed EBV-Negative Hodgkin Lymphoma by Targeting Upregulated MAGE-A4

Improving T-cell Therapy for Relapsed EBV-Negative Hodgkin Lymphoma by Targeting Upregulated MAGE-A4

Differential proteomic analysis of pathway biomarkers in human breast cancer by integrated bioinformatics

Prognostic roles of MAGE family�members in breast cancer based on KM‑Plotter Data

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