Ferroptosis-related alternative splicing signatures as potential biomarkers for predicting prognosis and therapy response in gastric cancer

• DOI: 10.1016/j.heliyon.2024.e34381
• Publication Date: 2024-07-11T00:35:01Z
• Authors: Gang Long; Zhiyong Li; Yue Gao; Xu Zhang; Xiyang Cheng; Irankunda Eric Da...; Lisha Zhang; Dawei Wang; Zhengtian Li
• Keywords: H1-99; 0301 basic medicine; 0303 health sciences; Science (General); Prognosis; Social sciences (General); Q1-390; Tumor microenvironment; Ferroptosis; Gastric cancer; Alternative splicing; Research Article

Ferroptosis is linked to various tumor biological traits, and alternative splicing (AS), a crucial step in mRNA processing, plays a role in the post-transcriptional regulation of ferroptosis-related genes (FRGs). A least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis was utilized to build a prognostic signature based on 12 AS events (p < 0.05), which was validated in gastric cancer (GC) patients. The high-risk group (n = 203) showed enrichment in cancer and metastasis pathways (p < 0.05). Significant differences existed between the high- and low-risk groups in terms of tumor microenvironment (TME) cell infiltration and immune activities (p < 0.05). The low-risk group (n = 203) was characterized by immune activation and improved prognosis (p < 0.001). Additionally, targeted treatment and immunotherapy were more likely to benefit the low-risk group (p < 0.05). Correlation analysis was performed to detect related splicing factors (SF) (Cor>0.4, FDR<0.05). Furthermore, our functional assay results suggested that high SF3A2 expression might increase ferroptosis resistance and promote cell proliferation. In conclusion, the FRAs model we built has an advantage in predicting GC prognosis. The model's demonstration of variations in the immune microenvironment and drug response could potentially inform decisions regarding treatment strategies.