Department of Statistics, School of Science, Wuhan University of Technology, 122 Luoshi Road, Wuhan, Hubei 430070, P. R. China.
Department of Biological Science and Technology, School of Chemistry Chemical Engineering and Life Sciences, Wuhan University of Technology Wuhan, Hubei, P. R. China.
J Bioinform Comput Biol. 2023 Aug;21(4):2350020. doi: 10.1142/S0219720023500208. Epub 2023 Sep 8.
Cancer is characterized by the dysregulation of alternative splicing (AS). However, the comprehensive regulatory mechanisms of AS in lung adenocarcinoma (LUAD) are poorly understood. Here, we displayed the AS landscape in LUAD based on the integrated analyses of LUAD's multi-omics data. We identified 13,995 AS events in 6309 genes as differentially expressed alternative splicing events (DEASEs) mainly covering protein-coding genes. These DEASEs were strongly linked to "cancer hallmarks", such as apoptosis, DNA repair, cell cycle, cell proliferation, angiogenesis, immune response, generation of precursor metabolites and energy, p53 signaling pathway and PI3K-AKT signaling pathway. We further built a regulatory network connecting splicing factors (SFs) and DEASEs. In addition, RNA-binding protein (RBP) mutations that can affect DEASEs were investigated to find some potential cancer drivers. Further association analysis demonstrated that DNA methylation levels were highly correlated with DEASEs. In summary, our results can bring new insight into understanding the mechanism of AS and provide novel biomarkers for personalized medicine of LUAD.
癌症的特征是可变剪接（AS）失调。然而，肺腺癌（LUAD）中 AS 的全面调控机制仍知之甚少。在这里，我们基于 LUAD 的多组学数据的综合分析，展示了 LUAD 中的 AS 图谱。我们在 6309 个基因中鉴定出 13995 个 AS 事件作为差异表达的可变剪接事件（DEASEs），主要涵盖编码蛋白的基因。这些 DEASEs 与“癌症特征”密切相关，如细胞凋亡、DNA 修复、细胞周期、细胞增殖、血管生成、免疫反应、前体代谢物和能量的产生、p53 信号通路和 PI3K-AKT 信号通路。我们进一步构建了连接剪接因子（SFs）和 DEASEs 的调控网络。此外，还研究了可能影响 DEASEs 的 RNA 结合蛋白（RBP）突变，以寻找一些潜在的癌症驱动因素。进一步的关联分析表明，DNA 甲基化水平与 DEASEs 高度相关。总之，我们的研究结果可以为理解 AS 的机制提供新的见解，并为 LUAD 的个体化医学提供新的生物标志物。
