Analysis of zebrafish homologs within the human genome provides valuable insights into exploring pan-cancer alternative splicing events as prognostic markers and therapeutic targets

Alternative splicing (AS) is pivotal in gene expression regulation and protein diversity generation. Suppression of aberrant AS holds promise in cancer management. Utilizing zebrafish-human homologous genes, we investigated AS events across 33 tumor types from TCGA, employing Cox regression analyses to identify prognostic AS events. A risk-scoring model distinguished high and low-risk groups, revealing differences in survival, tumor microenvironment, and immune cell infiltration. Notably, Complement C1q C Chain (C1QC), DENND5A, HP, IRF5, and LRP1 were associated with poor prognosis and immune infiltration. Mendelian randomization confirmed the protective role of C1QC across cancers, further supported by Bayesian Weighted Mendelian Randomization. Leveraging zebrafish homologs enhances our understanding of AS mechanisms and potential therapeutic targets in cancer biology.