A Comprehensive Analysis of Tn and STn Antigen Expression in Esophageal Adenocarcinoma

Simple Summary Esophageal adenocarcinoma is a type of cancer that originates in cells lining the lower part of the esophagus, the tube that connects the throat to the stomach. This cancer specifically arises from glandular cells, which produce mucus to help lubricate the lining of the esophagus. In this work, we investigated whether and to what extent truncated O-glycans, called Tn and STn antigens, are expressed under pathophysiological conditions and whether these correlate with clinicopathological data and overall survival. This investigation is particularly significant in the context of targeted therapies, since Tn and STn antigens are tumor-specific target structures.Abstract Differential glycosylation, marked by the presence of truncated O-glycans, is a distinctive feature of epithelial-derived cancers. However, there is a notable gap in research regarding the expression of Tn and STn antigens in esophageal adenocarcinoma (EAC). To address this, we employed commercially available antibodies, previously validated for Tn and STn antigens, to analyze two cohorts of EAC tissues. Initially, large-area tissue sections from formalin-fixed paraffin-embedded (FFPE) EAC and corresponding healthy tissues were subjected to immunohistochemistry (IHC) staining and scoring. Subsequently, we evaluated the RNA expression levels of crucial O-glycosylation related genes-C1GALT1 and C1GALT1C1-using a quantitative real-time polymerase chain reaction (qRT-PCR). In a comprehensive analysis, a substantial cohort of EAC tissues (n = 311 for Tn antigen, n = 351 for STn antigen) was investigated and correlated with clinicopathological data. Our findings revealed that Tn and STn antigens are highly expressed (approximately 71% for both) in EAC, with this expression being tumor-specific. Notably, Tn antigen expression correlates significantly with the depth of tumor cell infiltration (p = 0.026). These antigens emerge as valuable markers and potential therapeutic targets for esophageal adenocarcinoma.