GSDMA (Gasdermin A)

Notably, almost all infiltrating immune cells and immune checkpoints were negatively correlated with GSDMA/C/E expression and positively related to GSDMB/D and PJVK expression. We indicated the potential role of GSDMs (especially GSDME) in HNSC pathogenesis, progression and response to immunotherapy, providing important evidence for further prospective studies and molecular mechanism exploration.

Mechanistically, Gsdma1/2/3 depletion downregulated epidermal growth factor receptor (EGFR) ligands, leading to decreased EGFR-Stat3/Akt signalling. These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR-Stat3/Akt pathway.

In conclusion, our study demonstrates that high GSDMA expression in gliomas is associated with immune-infiltrating cells CD8 T cells and Treg cells, and indicates a worse prognosis in glioma. Therefore, GSDMA may serve as a therapeutic target for glioma progression and should be applied in immunotherapy for glioma patients.

Our data indicated that the heterogeneity of GSDM member expression exists at different cells, pathologic conditions, challenges, probably dependent upon cell biological phenomes, functions, and behaviors, upon cellular responses to external changes, and the nature and severity of lung disease. Thus, the deep exploration of GSDM phenomes may provide new insights into understanding the single-cell roles in the tissue, regulatory roles of the GSDM family in the pathogenesis, and potential values of biomarker identification and development.