MAGE-A gene expression in peripheral blood serves as a poor prognostic marker for patients with lung cancer.

BACKGROUND: MAGE-A genes belong to the cancer/testis antigens family. The prognostic significance of MAGE-A expression in the peripheral blood of patients with lung cancer is unknown. Therefore, this study evaluated the expression and possible prognostic significance of MAGE-A in the peripheral blood of patients with lung cancer. METHODS: In this study, we detected MAGE-A gene expression in the peripheral blood of 150 patients with lung cancer and 30 healthy donors using multiplex semi-nested PCR and analyzed their correlation with clinicopathological risk factors. RESULTS: MAGE-A expression was associated with factors indicating poor prognosis. The expression of MAGE-A and each individual MAGE-A gene were also associated with low overall survival in patients with lung cancer. CONCLUSION: The expression of MAGE-A genes in peripheral blood may act as a poor prognostic marker in patients with lung cancer.

Molecular evolution of type II MAGE genes from ancestral MAGED2 gene and their phylogenetic resolution of basal mammalian clades.

Type II melanoma-associated antigens (MAGE) are a subgroup of about a dozen proteins found in various locations in the genome and expressed in normal tissues, thus are not related to cancer as the type I MAGE genes. This gene family exists as a single copy in non-mammals and monotremata, but found as two copies in metatherians and occur as a diverse group in all eutherians. Our studies suggest MAGED2 as the ancestor of this subfamily and the most likely evolutionary history of eutherian type II MAGE genes is hereby proposed based on synteny conservation, phylogenetic relations, genome location, homology conservation, and the protein and gene structures. Type II genes can be divided into two: those with 13 exons (MAGED1, MAGED2, TRO, and MAGED4) and those with only one exon (MAGEE1, MAGEE2, MAGEF1, NSMCE3, MAGEH1, MAGEL2, and NDN) with different evolutionary patterns. Our results suggest a need to change the gene nomenclature to MAGE1 (the ancestral gene), currently designated as LOC103095671 and LOC100935086, in opossum and Tasmanian devil, respectively, and MAGE2 (the duplicated one), currently designated as LOC100617402 and NDNL2, respectively, to avoid confusion. We reconstructed the phylogenetic relationships among 23 mammalian species using the combined sequences of MAGED1, MAGED2, MAGEL2, and NDN, because of their high divergence, and found high levels of support, being able to resolve the phylogenetic relationships among Euarchontoglires, Laurasiatheria, Afrotheria, and Xenarthra, as an example that small, but phylogenetically informative sequences, can be very useful for resolving basal mammalian clades.

Evaluation of melanoma antigen (MAGE) gene expression in human cancers using The Cancer Genome Atlas.

Melanoma antigen (MAGE) cancer-testis (CT) (or cancer-germline) genes are frequently over-expressed in cancer. However, the types of cancer in which the MAGE genes are over-expressed and the effect of over-expression on outcomes have been difficult to ascertain, and their relevance to progression is unclear. We queried transcriptomic and survival data from 26 cancer studies through the cBio Cancer Genomics Portal (www.cbioportal.org) to investigate dysregulation of 34 MAGE genes in cancer. MAGE genes are dysregulated in many cancers. Up to 44% of samples had over-expression of 22 Type 1 MAGE, which are not expressed in most normal tissues, or dysregulation of 12 Type 2 MAGE genes, which are expressed in normal tissues. Dysregulation of specific MAGE genes correlated with reduced overall survival in four cancer types (brain low grade gliomas, renal clear cell carcinomas, head and neck squamous cell carcinomas, and uterine corpus endometrioid carcinomas), with weaker correlations in four additional cancer types. This study demonstrates (1) the value of cancer-germline antigen expression profiling as a complement to mutation analysis for prognosis in cancer; (2) that over-expression of MAGE genes in a subset of cancers is associated with reduced survival; and (3) that patterns of MAGE expression could inform individualized treatment in cancer.

Human melanoma metastases demonstrate nonstochastic site-specific antigen heterogeneity that correlates with T-cell infiltration.

PURPOSE: Metastasis heterogeneity presents a significant obstacle to the development of targeted cancer therapeutics. In this study, we sought to establish from a large series of human melanoma metastases whether there exists a determined pattern in tumor cellular heterogeneity that may guide the development of future targeted immunotherapies. EXPERIMENTAL DESIGN: From a cohort of 1,514 patients with metastatic melanoma, biopsies were procured over a 17-year period from 3,086 metastatic tumors involving various anatomic sites. To allow specific tumor cell profiling, we used established immunohistochemical methods to perform semiquantitative assessment for a panel of prototypic melanocyte differentiation antigens (MDA), including gp100, MART-1, and tyrosinase. To gain insight into the endogenous host immune response against these tumors, we further characterized tumor cell expression of MHC I and MHC II and, also, the concomitant CD4(+) and CD8(+) T-cell infiltrate. RESULTS: Tumor cell profiling for MDA expression demonstrated an anatomic site-specific pattern of antigen expression that was highest in brain, intermediate in soft tissues/lymph nodes, and lowest in visceral metastases. Hierarchical clustering analysis supported that melanoma metastases have a phylogenetically determined, rather than a stochastic, pattern of antigen expression that varies by anatomic site. Furthermore, tyrosinase expression was more frequently lost in metastatic sites outside of the brain and was uniquely correlated with both endogenous CD8(+) and CD4(+) T-cell infiltrates. CONCLUSION: Site-specific antigen heterogeneity represents a novel attribute for human melanoma metastases that should be considered in future therapy development and when assessing the responsiveness to antigen-specific immunotherapies.

Melanoma-associated antigen genes - an update.

To date, dozens of melanoma-associated antigens (MAGE) have been identified. Based on the differences in tissue-specific gene expression and gene structure, the MAGE family has been divided into two big subfamilies: MAGE-I and MAGE-II. MAGE-I genes were identified as a group of highly attractive targets for cancer immunotherapy because of their wide expression in a variety of malignant tumors but silent in normal adult cells except germ-line cells lacking human leukocyte antigen (HLA) expression. However, little is known regarding the functions of MAGE family members in cell activities. In this review, we briefly described the classification of MAGE family members and their expression pattern in cancer. We also summarized the mechanism of MAGE activation and the functions of MAGE family members in cell cycle progression and apoptosis. We also discussed what is known of immunotherapy targeting MAGE family.