Correlation Analysis of Pyroptosis-Related Genes CASP1, NLRP3, AIM2, and NLRP1 With Lung Adenocarcinoma

Purpose: This study is aimed at exploring the role of pyroptosis-related genes in the development, immune infiltration, and clinical features of lung adenocarcinoma.

Method: Pyroptosis-related genes were searched using online databases, including MSigDB, Gene, and GeneCards. We explored pyroptosis-related gene expression patterns in lung adenocarcinoma using the UALCAN database. Functional enrichment analysis of pyroptosis-related genes in lung adenocarcinoma was performed using the Metascape database. A protein–protein interaction network was constructed using the STRING database, and the outcomes were visualized using Cytoscape. The top five core genes were screened utilizing the MCC algorithm with its cytoHubba plugin. The correlation between immune cell infiltration, diagnosis, and prognosis of core genes in lung adenocarcinoma was explored using the TIMER 2.0, TCGA, and Kaplan–Meier plotter databases. A nomogram was constructed to predict the survival of patients with lung adenocarcinoma using Cox regression analysis, and its clinical value was validated. Samples of paraffin-embedded lung adenocarcinoma tissues were collected and subjected to immunohistochemical tests to verify the expression of core genes in lung adenocarcinoma and adjacent tissues.

Results: Overall, 202 genes related to pyroptosis were identified, with 67 upregulated and 60 downregulated in lung adenocarcinomas. The top five core genes—namely, CASP1 (caspase1), PYCARD (PYD and CARD domain-containing protein), NLRP3 (NOD-like receptor protein 3), AIM2 (absent in melanoma 2), and NLRP1 (NOD-like receptor protein 1)—related to lung adenocarcinoma pyroptosis were selected. The correlation analysis of immune cell infiltration showed that CASP1, NLRP3, and AIM2, which showed that pyroptosis was involved in the infiltration of immune cells in the tumor microenvironment and NLRP1 exhibited high diagnostic efficacy, while PYCARD demonstrated poor diagnostic efficacy. High expression of CASP1, NLRP3, and NLRP1 correlated with a better prognosis (p < 0.05), while elevated AIM2 expression was associated with a poor prognosis (p < 0.05). However, PYCARD exhibited no significant correlation with prognosis (p > 0.05). The immunohistochemistry results showed that positive rates of CASP1, NLRP3, AIM2, and NLRP1 were 20%, 15%, 70%, and 10%, respectively, while in adjacent tissues, the positive rates were 60%, 60%, 20%, and70%, indicating high expression of AIM2 and low expression of CASP1, NLRP3, and NLRP1 in lung adenocarcinoma.

Conclusion: CASP1, NLRP3, AIM2, and NLRP1 are core pyroptotic genes in lung adenocarcinoma and exhibit a strong correlation with immune cell infiltration, diagnosis, and prognosis of this condition. These genes may be useful in the clinical diagnosis and treatment of patients with lung adenocarcinoma.