Association of the TGFβ gene family with microenvironmental features of gastric cancer and prediction of response to immunotherapy

Abstract

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.