Department of Clinical Laboratory, Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Wenzhou, Zhejiang, China (mainland).
Department of Respiratory and Critical Care Medicine, Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Wenzhou, Zhejiang, China (mainland).
Med Sci Monit. 2021 Dec 5;27:e934491. doi: 10.12659/MSM.934491.
BACKGROUND The exact mechanisms of lung adenocarcinoma (LUAD) etiology and pathogenesis remain unclear. MATERIAL AND METHODS In this study, we evaluated alternative splicing (AS) events in LUAD. We separately analyzed LUAD data from The Cancer Genome Atlas (TCGA) database and AS-related feature lists from SpliceSeq to develop risk models for AS events and further validated risk models for AS events. The association between immune-related features and the risk model of AS events was evaluated. RESULTS We found that exon skip (ES) and mutually exclusive exons (ME) exhibited the most and least AS events, respectively. The risk score and stage of LUAD patients were strongly associated with prognosis and were independent influences on the prognosis of LUAD. The pathological stage (stage, T, N) and risk model were incorporated to construct a column line graph with better predictive ability. Risk models were associated with tumor microenvironment, and higher risk score values were associated with higher M2 macrophage content and lower M0 macrophage and helper T lymphocyte content. The correlation between core genes and immunity was further assessed by analyzing differentially-expressed genes between risk models. These results suggest an association between the level of risk for AS events and the density of immune cell infiltration. CONCLUSIONS Our findings suggest a clear association between AS risk model and patient prognosis, and was performed to confirm the biological relationship between AS and immunity.
肺腺癌（LUAD）的发病机制仍不清楚。
本研究评估了 LUAD 的可变剪接（AS）事件。我们分别分析了来自癌症基因组图谱（TCGA）数据库的 LUAD 数据和 SpliceSeq 的 AS 相关特征列表，以开发 AS 事件的风险模型，并进一步验证了 AS 事件的风险模型。评估了免疫相关特征与 AS 事件风险模型之间的关系。
我们发现外显子跳跃（ES）和互斥外显子（ME）分别具有最多和最少的 AS 事件。LUAD 患者的风险评分和分期与预后密切相关，是 LUAD 预后的独立影响因素。将病理分期（分期、T、N）和风险模型结合起来构建列线图，具有更好的预测能力。风险模型与肿瘤微环境相关，较高的风险评分值与较高的 M2 巨噬细胞含量和较低的 M0 巨噬细胞和辅助 T 淋巴细胞含量相关。通过分析风险模型之间差异表达基因，进一步评估了核心基因与免疫之间的相关性。这些结果表明 AS 事件风险模型与免疫细胞浸润密度之间存在关联。
我们的研究结果表明，AS 风险模型与患者预后之间存在明显的关联，并对 AS 与免疫之间的生物学关系进行了验证。
