Cancer/testis antigen expression and co-expression patterns in Gastroesophageal Adenocarcinoma

TL;DR

This study explores cancer/testis antigens in gastroesophageal adenocarcinoma, finding they are commonly expressed and may be useful for new therapies.

Contribution

The study identifies co-expression patterns of CTAs in GEAC and suggests potential for multi-targeted therapies.

Findings

CTAs, especially the MAGE gene family, are highly expressed in gastroesophageal adenocarcinoma.

MAGEA3, NY-ESO-1, and others show strong co-expression, suggesting potential for combined therapeutic targeting.

CTA expression correlates with survival outcomes, particularly in patients receiving immunotherapy.

Abstract

Gastroesophageal adenocarcinoma (GEAC) poses a significant challenge due to its poor prognosis and limited treatment options. Recently, Cancer/testis antigens (CTAs) have emerged as potential therapy targets due to their high expression in tumor cells and their immunogenic nature. We aimed to explore the expression and co-expression of CTAs in GEAC. We analyzed 63 GEAC patients initially and validated our findings in 329 patients from The Cancer Genome Atlas (TCGA) database. CTA expression was measured after RNA sequencing, while clinical information, including survival outcomes and treatment details, was collected from an institutional database. Co-expression patterns among CTAs were determined using Pearson correlation analysis. The majority of the study cohort were male (87%), Caucasian (94%), and had stage IV disease (64%). CTAs were highly prevalent, ranging from 58–19%. The MAGE gene family showed the highest expression, consistent across both cohorts. The correlation matrix revealed a distinct cluster of significantly co-expressed genes, including MAGEA3, NY-ESO-1, and others (0.27 ≤ r ≤ 0.73). Survival analysis revealed that individual CTAs were associated with poorer survival outcomes in patients not receiving immunotherapy while showing potential for improved survival in those undergoing immunotherapy, although these findings lacked robust reliability. Our study provides a comprehensive characterization of CTA expression and co-expression in GEAC. The strong correlation among CTAs like MAGE, NY-ESO-1, and GAGE suggests a potential for therapies targeting multiple CTAs simultaneously. Further research, including prospective trials, is warranted to assess the prognostic value of CTAs and their suitability as therapeutic targets.

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