摘要

TGF beta signaling plays a key role in cancer progression and by shaping tumor architecture and inhibiting the anti-tumor activity of immune cells. It was reported that high expression of TGF beta can promote the invasion and metastasis of cancer cells in a variety of tumors. However, there are few studies on TGF beta 2 and its methylation in gastric cancer. We analyzed the Harbin Medical University Cancer Hospital (HMUCH) sequencing data and used public data to explore the potential function and prognostic value of TGF beta 2 and its methylation in gastric cancer. In this study, we used the ssGSEA algorithm to quantify 23 methylation sites related to TGF beta 2. Survival analysis showed that high expression of TGF beta 2 and hypomethylation levels of TGF beta 2 were negative factors in the prognosis of gastric cancer. Functional enrichment analysis of methylation revealed that methylation of different TGF beta 2 methylation scores was mainly involved in energy metabolism, extracellular matrix formation and cell cycle regulation. In the gastric cancer microenvironment TGF beta 2 was associated with high levels of multiple immune cell infiltration and cytokine expression, and high TGF beta 2 expression was significantly and positively correlated with stemness markers, stromalscore and EMT. Gene set enrichment analysis also revealed an important role of TGF beta 2 in promoting EMT. In addition, we discussed the relationship between TGF beta 2 and immunotherapy. The expression of PD-1, PD-L1 and CTLA-4 was elevated in the TGF beta 2 high expression group. Also when TGF beta 2 was highly expressed, the responsiveness of immune checkpoint blockade (ICB) was significantly enhanced. This indicates that TGF beta 2 may become an indicator for predicting the efficacy of immunosuppressive agents and a potential target for immunotherapy.

  • 单位
    哈尔滨医科大学