The clinical significance of MAGEA3 expression in pancreatic cancer

Abstract

The MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intentto-cure surgery for PDAC. Total RNA from paraffin-embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe-based quantitative real-time RT-PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log-rank, p 5 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0-4.4, p 5 0.041; and HR 3.7, 95% CI: 1.8-7.6, p 5 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune-based therapy. ' 2005 Wiley-Liss, Inc.

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

“…This is in agreement with recent findings in other cancers showing that CT-X gene expression is often coordinated due to hypomethylation of their promoters (50,51). In addition, CT-X gene expression in patients with epithelial cancers is often associated with a poor patient outcome (52)(53)(54). Our data are also in agreement with recent studies emphasizing that the MMC of patients that express MAGE-C1, MAGE-A3, and/or NY-ESO-1 had an increased proliferative activity and are obtained mainly from patients with stage III MM (32,40).…”

Epigenetic Control in Pituitary Tumors

“…The MAGE-I family consists of a number of chromosome X-clustered genes, which are expressed mainly in testicular germ cells, placenta, and a variety of malignant tumors, resulting in their designation as Cancer/Testis antigens [33][34][35][36][37]. Our new data describe the presence of MAGE-A3 transcripts in pituitary tumors.…”

Mage-A Cancer/Testis Antigens Inhibit p53 Function by Blocking Its Interaction with Chromatin

“…If those same cancer cells also express Mage-A proteins they may well have a broad ranging effect on p53 function. Finally, if Mage-A proteins, which are generally associated with the onset of aggressive characteristics in tumors (6,(8)(9)(10)(11)(12)(13), are indeed able to inhibit wild-type p53 in developing tumors, analysis of tumor specimens should reveal associations that support this model. In addition, targeting of the p53/Mage-A interaction may have significant impact as part of the therapeutic arsenal and would be highly specific for tumor cells, given that Mage-A proteins are only expressed physiolgically in germ cells.…”

“…The Mage-A (melanoma antigen) proteins form a 12-member subgroup of the CT family that show striking identity with each other and are encoded as a cluster at the Xq28 region (7). Mage-A proteins are expressed in several types of cancer, including melanoma, breast, nonsmall cell lung cancer, pancreatic cancer, and ovarian carcinomas, and are especially associated with invasion, metastasis, and poor patient survival (6,(8)(9)(10)(11)(12)(13). The normal physiologic role of Mage-A proteins remains unknown and their contribution to the development of cancer cells is poorly understood.…”