Prognostic alternative splicing events related splicing factors define the tumor microenvironment and pharmacogenomic landscape in lung adenocarcinoma

Background: Recent studies identified correlations between splicing factors (SFs) and tumor progression and therapy. However, the potential roles of SFs in immune regulation and the tumor microenvironment (TME) remain unknown. Methods: We used UpSet plots to screen for prognostic-related alternative splicing (AS) events. We evaluated SF patterns in specific immune landscapes. Single sample gene set enrichment analysis (ssGSEA) algorithms were used to quantify relative infiltration levels in immune cell subsets. Principal component analysis (PCA) algorithm-based SFscore were used to evaluate SF patterns in individual tumors with an immune response. Results: From prognosis-related AS events, 16 prognosis-related SFs were selected to construct three SF patterns. Further TME analyses showed these patterns were highly consistent with immune-inflamed, immune-excluded, and immune-desert landscapes. Based on SFscore constructed using differentially expressed genes (DEGs) between SF patterns, patients were classified into two immune-subtypes associated with differential pharmacogenomic landscapes and cell features. A low SFscore was associated with high immune cell infiltration, high tumor mutation burden (TMB), and elevated expression of immune check points (ICPs), indicating a better immune response. Conclusions: SFs are significantly associated with TME remodeling. Evaluating different SF patterns enhances our understanding of the TME and improves effective immunotherapy strategies.