Background. The leading cause of cancer-related fatalities globally is lung cancer; lung adenocarcinoma (LUAD) is the most common histological type in it. The spliceosome plays an important role in a majority of malignancies. However, it is yet unclear how spliceosome-related genes affect patients with LUAD in terms of treatment course and prognosis. Methods. Spliceosome-related genes were assessed from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database to obtain clinical information and gene expression in patients with LUAD. A spliceosome-related gene signature and prognostic model were constructed by using the least absolute shrinkage and selection operator (LASSO), time-dependent receiver operating characteristic (ROC), and nomogram. Immune infiltrate levels, mutation analysis, and pathway enrichment were predicted potential mechanisms of the signature by using single-sample gene set enrichment analysis (ssGSEA), Gene Set Cancer Analysis (GSCA) database, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) database. Then, a protein–protein interaction (PPI) network and transcription factor- (TF-) hub gene and drug mining network were also established by Cytoscape software. Results. Firstly, we constructed a prognostic model for 11 spliceosome signature genes. Based on the prognostic risk score, we stratified patients with LUAD into high- and low-risk groups. The high- and low-risk groups were closely related to the OS, tumor immune infiltration level, immune checkpoint molecules, and tumor mutation burden (TMB) of LUAD patients. Based on PPI networks, we also predict relevant TF genes that may regulate signature prognostic genes. Finally, drugs including oxaliplatin, arsenic trioxide, cisplatin, and sunitinib were excavated for the treatment of the 11 spliceosome signature genes in LUAD patients. Conclusion. In conclusion, this study is the first to explore the importance of spliceosome-related genes in the prognosis and treatment of LUAD. Through our study, we have innovatively provided potential prognosis genes and new therapeutic drug targets for the treatment of LUAD patients.

中文翻译：

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剪接体相关基因预测肺腺癌预后及治疗策略的意义

背景。全球癌症相关死亡的主要原因是肺癌；肺腺癌（LUAD）是其中最常见的组织学类型。剪接体在大多数恶性肿瘤中起着重要作用。然而，目前尚不清楚剪接体相关基因如何影响 LUAD 患者的治疗过程和预后。方法. 从癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据库评估剪接体相关基因，以获得 LUAD 患者的临床信息和基因表达。通过使用最小绝对收缩和选择算子 (LASSO)、时间依赖性接受者操作特征 (ROC) 和诺模图构建了剪接体相关基因特征和预后模型。通过使用单样本基因集富集分析 (ssGSEA)、基因集癌症分析 (GSCA) 数据库、京都基因与基因组百科全书 (KEGG) 和基因本体论 (GO) 数据库。然后，结果。首先，我们构建了 11 个剪接体特征基因的预后模型。根据预后风险评分，我们将 LUAD 患者分为高风险组和低风险组。高危和低危人群与LUAD患者的OS、肿瘤免疫浸润水平、免疫检查点分子、肿瘤突变负荷（TMB）密切相关。基于 PPI 网络，我们还预测了可能调节标志性预后基因的相关 TF 基因。最后，挖掘了包括奥沙利铂、三氧化二砷、顺铂和舒尼替尼在内的药物用于治疗 LUAD 患者的 11 个剪接体特征基因。结论. 总之，本研究首次探讨剪接体相关基因在LUAD预后和治疗中的重要性。通过我们的研究，我们创新性地为LUAD患者的治疗提供了潜在的预后基因和新的治疗药物靶点。