Abstract Background Pyroptosis is a recently identified form of programmed cell death that plays a pivotal role in the initiation and progression of cancer. However, the function of focal death in lung adenocarcinoma (LUAD) remains uncertain. The objective of this study was to integrate proteomics data with single-cell RNA sequence (scRNA-seq) in order to investigate the potential role of pyroptosis-related proteins (PRPs) within the tumor microenvironment (TME) and their relationship with tumor immunity, prognosis, and therapeutic response. Methods A comprehensive proteomic analysis was conducted on 103 lung adenocarcinoma patients. ScRNA-seq data was integrated with a bioinformatics approach for prognostic and immunological analyses. Three clusters were obtained after unsupervised clustering based on the PRPs, while GSEA was later used for functional analysis and TME and CIBERSORT algorithms for immune infiltration analysis. Subsequently, functional enrichment analysis, immune infiltration analysis, and cellular communication analysis were conducted on the scRNA-seq data, grouped according to the proteomic clusters. A PRP related prognostic score was constructed using LASSO-Cox regression. The expression of the selected PRPs was validated in pathological specimens. Results We identified multiple PRP alterations that correlated with clinicopathologic features, prognosis, and TME cell infiltration characteristics of patients. Our analysis revealed three distinct molecular subtypes: lipid metabolism, signaling transduction, and immune activation. Of these, the lipid metabolism subtype exhibited the most favorable prognosis. Single-cell RNA-seq data analysis supported immune characterization of the three subtypes and predicted cellular interaction networks and ligand-receptor profiles. A PRP score predicting overall survival was then constructed and validated for its predictive ability in LUAD patients. Furthermore, in our analysis of LUAD, we found that the PRP score was significantly correlated with tumor immunity and chemotherapeutic drug sensitivity. Conclusion Our comprehensive analysis of PRPs in proteomics data and single-cell transcriptomic data from LUAD demonstrates their potential role in the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. These findings could enhance our comprehension of PRPs in LUAD and open up new avenues for assessing prognosis and creating more efficient immunotherapeutic approaches. This abstract is funded by: None
Wei et al. (Fri,) studied this question.