MAGEA Family Gene Expression Influences Survival in Intestinal-Type Gastric Cancer

Gastric cancer (GC) is a heterogeneous disease characterized by diverse molecular profiles and distinct histological subtypes, each with differing prognoses and therapeutic responses. Melanoma-associated antigen-A (MAGEA) genes encode cancer testis antigens frequently expressed in tumor tissue and in limited amounts in normal tissues, making them a promising target for cancer immunotherapy. While therapies targeting MAGEA family members have demonstrated promise across various cancers, clinical trials have been limited by substantial toxicities, underscoring the need to precisely identify patient subgroups most likely to benefit from MAGEA-targeted treatments. We performed gene expression analysis of MAGEA3, 6 and 12 in an Australian-based multicenter cohort of 100 GC patients, including 49 intestinal-type GC cases accrued between 1999 and 2009, and compared expression profiles with those of the Cancer Genome Atlas (TCGA) cohort. Expression patterns were determined in histological and TCGA molecular subtypes of GC. Progression-free survival was examined using the log-rank test and Cox proportional hazards modeling. MAGEA3, 6, and 12 were mainly expressed in intestinal-type GC and were not associated with other clinicopathological variables. Multivariate analyses revealed that elevated expression of these MAGEA members was prognostic of poorer survival in intestinal-type GC patients. In the TCGA cohort, higher MAGEA3, 6, and 12 expression was observed in intestinal-type GC and the chromosomal instability (CIN) subtype, and associations of poorer progression-free survival with high expression were found. Our findings highlight the differences in GC subtype biology and suggest a potential role for MAGEA3, 6, and 12 as biomarkers and targets for intestinal-type GC immunotherapy; however, the relatively small intestinal-type GC sample size warrants validation in larger cohorts.