2023 World Conference on Lung Cancer (Posters)-EP11.01. GSDME-dependent Pyroptosis Affects the Prognosis and Response to Immunotherapy in Lung Adenocarcinoma

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Researchers from Tianjin Medical University General Hospital in China have discovered a potential link between pyroptosis, a form of cell death, and the prognosis of and response to immunotherapy in patients with lung adenocarcinoma (LUAD). The immune microenvironment of LUAD is known to be rich in immune cells, and pyroptotic cells release inflammatory factors that can reshape the immune microenvironment. However, the relationship between pyroptosis and LUAD has not been fully understood until now.<br /><br />The researchers used RNA expression data from LUAD patients to identify six prognostic-related differentially expressed genes (DEGs) using univariate cox regression. These DEGs were then used to construct a prognostic model, and further analysis narrowed it down to five DEGs. Validation data from another database confirmed the accuracy of the model.<br /><br />Based on consistent clustering analysis of the five DEGs, the researchers were able to divide LUAD patients into three clusters, with cluster 3 showing significantly poorer prognosis compared to the other two clusters. Immune function analysis revealed that cluster 3 had a higher immune score and showed more infiltration of macrophages and Treg cells, suggesting a potentially suppressed immune response.<br /><br />Further investigation into pyroptosis-related proteins found that the expression of GSDME, a protein associated with pyroptosis, was higher in cluster 3. This suggests that GSDME-dependent pyroptosis is the main form of pyroptosis in cluster 3.<br /><br />To validate their findings, the researchers analyzed data from patients who received anti-PD1 immunotherapy and found that those who responded to the treatment had lower expression levels of HMGB1, a protein associated with pyroptosis. In laboratory experiments using lung cancer cell lines, the researchers induced pyroptosis and found an increase in HMGB1 secretion. However, when GSDME expression was suppressed, the increase in HMGB1 secretion was also inhibited, indicating that GSDME-dependent pyroptosis is associated with increased HMGB1 secretion.<br /><br />Overall, these findings suggest that GSDME-dependent pyroptosis may be linked to poor prognosis in LUAD patients and could affect the response to anti-PD1 immunotherapy. The researchers propose using pyroptosis-related genes as a model to predict the prognosis of LUAD patients.

Asset Subtitle

Peijun Cao

Meta Tag

Speaker Peijun Cao

Topic Metastatic NSCLC: Immunotherapy - Biomarker

Keywords

pyroptosis

cell death

prognosis

immunotherapy

lung adenocarcinoma

LUAD

immune microenvironment

differentially expressed genes

GSDME

HMGB1 secretion