Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Berlin Institute of Health at Charité Universitätsmedizin Berlin, Charitéplatz1, 10117, Berlin, Germany.
BMC Cancer. 2022 Sep 5;22(1):953. doi: 10.1186/s12885-022-10016-5.
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.
Tissue from a retrospective cohort of 277 patients with AEG/AS treated primarily by surgery at the Charité - Universitätsmedizin 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.
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.
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.
食管（AEG）和胃（AS）腺癌是世界上最常见的癌症之一。强烈需要新的标志物来进行风险分层和指导治疗。激活素是一种多功能细胞因子，具有特定的促肿瘤和抗肿瘤作用。我们旨在研究激活素肿瘤蛋白表达在 AEG/AS 中的预后作用。
我们收集了来自柏林夏洛蒂医科大学（Charité - Universitätsmedizin Berlin）的 277 名接受主要手术治疗的 AEG/AS 患者的回顾性队列的组织，并使用针对激活素同源二聚体抑制素β A 的特异性抗体通过免疫组织化学进行分析。此外，我们还评估了 T 细胞浸润和 PD1 表达以及免疫组织化学表达 PD-L1 作为可能的混杂因素。收集临床病理数据并与激活素蛋白表达相关联。
在 277 个肿瘤样本中，有 72 个（26.0%）表现出高激活素亚单位抑制素β A 蛋白表达。较高的表达与较低的国际癌症控制联盟（UICC）分期和更长的总生存期相关。有趣的是，激活素亚单位表达与 CD4 T 细胞浸润相关，并且与更高的总生存期的相关性仅见于高 CD4 T 细胞浸润的肿瘤中，这表明激活素在 AEG/AS 中的肿瘤免疫反应中发挥作用。
在我们的 AEG/AS 队列中，较高的激活素亚单位水平与更长的总生存期相关，这种作用仅见于 CD4 细胞浸润较高的肿瘤中。需要进一步的机制研究来辨别这种特定于上下文的细胞因子的确切作用。
