Han Bangling, Fang Tianyi, Zhang Yao, Zhang Yongle, Gao Jialiang, Xue Yingwei
Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Front Oncol. 2022 Sep 2;12:920599. doi: 10.3389/fonc.2022.920599. eCollection 2022.
In the complex tumor microenvironment, TGFβ is a pleiotropic cytokine involved in regulating cellular processes such as cancer cell proliferation, apoptosis and metastasis. TGFβ defines three subtypes (TGFβ1, TGFβ2, and TGFβ3), of which TGFβ is highly expressed in many cancers, especially those showing high dissemination potential. In addition, increased expression of TGFβ in multiple cancers is usually positively correlated with epithelial mesenchymal transition (EMT) and coordinated with the expression of genes driving EMT-related genes. TGFβ signaling in the tumor microenvironment inhibits the antitumor function of multiple immune cell populations, including T cells and natural killer cells, and the resulting immunosuppression severely limits the efficacy of immune checkpoint inhibitors and other immunotherapeutic approaches. As a major pathway to enhance the efficacy of cancer immunotherapy effects, the role of TGFβ signaling inhibitors have been evaluated in many clinical trials. However, the potential functions and mechanisms of TGFβ1, TGFβ2 and TGFβ3 in gastric cancer progression and tumor immunology are unclear. In this study, we comprehensively analyzed TGFβ1, TGFβ2 and TGFβ3 and gastric cancer microenvironmental features, including immune cell infiltration, EMT, hypoxia, mutation, immunotherapy and drug treatment, based on HMUCH sequencing data (GSE184336) and public databases. We also validated the protein expression levels of TGFβ in gastric cancer tissues as well as the role of TGFβ factor in cytology experiments. This report reveals the important role of the TGFβ gene family in gastric cancer and provides possible relationships and potential mechanisms of TGFβ in gastric cancer.
在复杂的肿瘤微环境中，转化生长因子β（TGFβ）是一种多效性细胞因子，参与调节诸如癌细胞增殖、凋亡和转移等细胞过程。TGFβ有三种亚型（TGFβ1、TGFβ2和TGFβ3），其中TGFβ在许多癌症中高表达，尤其是那些具有高扩散潜力的癌症。此外，多种癌症中TGFβ表达的增加通常与上皮-间质转化（EMT）呈正相关，并与驱动EMT相关基因的基因表达协调一致。肿瘤微环境中的TGFβ信号传导抑制多种免疫细胞群体（包括T细胞和自然杀伤细胞）的抗肿瘤功能，由此产生的免疫抑制严重限制了免疫检查点抑制剂和其他免疫治疗方法的疗效。作为增强癌症免疫治疗效果的主要途径，TGFβ信号传导抑制剂的作用已在许多临床试验中得到评估。然而，TGFβ1、TGFβ2和TGFβ3在胃癌进展和肿瘤免疫学中的潜在功能和机制尚不清楚。在本研究中，我们基于HMUCH测序数据（GSE184336）和公共数据库，全面分析了TGFβ1、TGFβ2和TGFβ3以及胃癌微环境特征，包括免疫细胞浸润、EMT、缺氧、突变、免疫治疗和药物治疗。我们还验证了胃癌组织中TGFβ的蛋白表达水平以及TGFβ因子在细胞学实验中的作用。本报告揭示了TGFβ基因家族在胃癌中的重要作用，并提供了TGFβ在胃癌中的可能关系和潜在机制。
