Prognostic impact of activin subunit inhibin beta A in gastric and esophageal adenocarcinomas

Purpose: Adenocarcinomas of the esophagus (AEG) and stomach (AS) are among the most common cancers worldwide. Novel markers for risk stratification and guiding treatment are strongly needed. Activin is a multi-functional cytokine with context specific pro- and anti-tumorigenic effects. We aimed to investigate the prognostic role of activin tumor protein expression in AEG/ASs. Methods: Tissue from a retrospective cohort of 277 patients with AEG/AS treated primarily by surgery at the Charite - Universitatsmedizin Berlin was collected and analyzed by immunohistochemistry using a specific antibody to the activin homodimer inhibin beta A. Additionally, we evaluated T-cell infiltration and PD1 expression as well as expression of PD-L1 by immunohistochemistry as possible confounding factors. Clinico-pathologic data were collected and correlated with activin protein expression. Results: Out of 277 tumor samples, 72 (26.0%) exhibited high activin subunit inhibin beta A protein expression. Higher expression was correlated with lower Union for International Cancer Control (UICC) stage and longer overall survival. Interestingly, activin subunit expression correlated with CD4(+) T-cell infiltration, and the correlation with higher overall survival was exclusively seen in tumors with high CD4(+) T-cell infiltration, pointing towards a role of activin in the tumor immune response in AEG/ASs. Conclusion: In our cohort of AEG/AS, higher activin subunit levels were correlated with longer overall survival, an effect exclusively seen in tumors with high CD4(+) cell infiltration. Further mechanistic research is warranted discerning the exact effect of this context specific cytokine.

Automated summary

This study aimed to investigate the prognostic role of activin tumor protein expression in esophageal and gastric adenocarcinomas. The results showed that higher levels of activin subunits were associated with lower cancer stage and longer overall survival. Furthermore, tumors with higher activin subunit expression also had higher CD4(+) T-cell infiltration, and the longer overall survival effect was only observed in tumors with high CD4(+) T-cell infiltration.