Gastric Adenocarcinomas with CDX2 Induction Show Higher Frequency of TP53 and KMT2B Mutations and MYC Amplifications but Similar Survival Compared with Cancers with No CDX2 Induction

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Background: Gastric cancer is one of the most prevalent gastrointestinal cancers. Mortality is high, and improved treatments are needed. A better understanding of the pathophysiology of the disease and discovery of biomarkers for targeted therapies are paramount for therapeutic progress. CDX2, a transcription factor of hindgut specification, is induced in several gastric cancers, especially with intestinal differentiation, and could be helpful for defining sub-types with particular characteristics. Methods: Gastric cancers with induced CDX2 mRNA expression were identified from the gastric cohort of The Cancer Genome Atlas (TCGA) and were compared with cancers that had no CDX2 mRNA induction. Induced CDX2 mRNA expression was defined as mRNA expression z-score relative to all samples above 0, and non-induced CDX2 mRNA expression was defined as mRNA expression z-score relative to all samples below −1. Results: Patients with gastric cancers with CDX2 mRNA induction were older, had less frequently diffuse histology, and more often had mutations in TP53 and KMT2B and amplifications in MYC. CDX2 induction was correlated with HNF4α induction and was reversely correlated with SOX2. Gastric cancers with CDX2 mRNA induction showed lower PD-L1 expression than cancers with lower CDX2 expression but did not differ in CLDN18 mRNA expression. Progression-free and overall survival of the two groups was also not significantly different. Conclusion: Gastric cancers with CDX2 mRNA induction displayed specific characteristics that differentiate them from cancers with no CDX2 induction and could be of interest for optimizing current and future therapies.