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

EP11.01. GSDME-dependent Pyroptosis Affects the Prognosis and Response to Immunotherapy in Lung Adenocarcinoma - PDF(Abstract)

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This study aimed to explore the relationship between pyroptosis, a type of cell death characterized by the release of inflammatory factors, and the prognosis and response to immunotherapy in lung adenocarcinoma (LUAD) patients. The researchers used LUAD patient RNA expression data from the TCGA database and identified 5 pyroptosis-related genes to construct a prognostic model. They then used consistent clustering analysis to divide LUAD patients into three clusters, with cluster 3 showing a significantly worse prognosis compared to the other two clusters. Cluster 3 also had higher immune scores and more macrophage and Treg cell infiltration.<br /><br />Furthermore, the study found that the expression of GSDME, a protein involved in pyroptosis, was higher in cluster 3, suggesting that GSDME-dependent pyroptosis is the main form of pyroptosis in this cluster. The researchers also analyzed data from LUAD patients who received immunotherapy and found that lower expression levels of HMGB1, a protein associated with inflammation, were observed in patients who responded to anti-PD1 therapy.<br /><br />In cell line experiments, the researchers induced pyroptosis and observed an increase in HMGB1 secretion. However, when GSDME expression was reduced using small interfering RNA, the increase in HMGB1 was inhibited. This suggests that GSDME-dependent pyroptosis is associated with increased HMGB1 secretion.<br /><br />Based on their findings, the researchers propose a prognostic model for LUAD patients based on pyroptosis-related genes. They also suggest that GSDME-dependent pyroptosis may contribute to poor prognosis and ineffectiveness of anti-PD1 treatment in LUAD patients. Overall, this study highlights the potential role of pyroptosis and GSDME in the prognosis and response to immunotherapy in LUAD.

Asset Subtitle

Peijun Cao

Meta Tag

Speaker Peijun Cao

Topic Metastatic NSCLC: Immunotherapy - Biomarker

Keywords

pyroptosis

prognosis

immunotherapy

lung adenocarcinoma

gene expression

TCGA database

clustering analysis

immune scores

GSDME

HMGB1