Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Medcine, Qingdao University, Qingdao, China.
BMC Pulm Med. 2021 Dec 6;21(1):400. doi: 10.1186/s12890-021-01776-0.
Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide due to the lack of early diagnostic markers and specific drugs. Previous studies have shown the association of LUAD growth with aberrant alternative splicing (AS). Herein, clinical data of 535 tumor tissues and 59 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. Each sample was analyzed using the ESTIMATE algorithm; a comparison between higher and lower score groups (stromal or immune) was made to determine the overall- and progression-free survival-related differentially expressed AS (DEAS) events. We then performed unsupervised clustering of these DEASs, followed by determining their relationship with survival rate, immune cells, and the tumor microenvironment (TME). Next, two prognostic signatures were developed using bioinformatics tools to explore the prognosis of cases with LUAD. Five OS- and six PFS-associated DEAS events were implemented to establish a prognostic risk score model. When compared to the high-risk group (HRG), the PFS and OS of the low-risk group (LRG) were found to be considerable. Additionally, a better prognosis was found considerably associated with the ESTIMATE score of the patients as well as immune cells infiltration. Our analysis of AS events in LUAD not only helps to clarify the tumorigenesis mechanism of AS but also provides ideas for revealing potential prognostic biomarkers and therapeutic targets.
肺腺癌 (LUAD) 是全球癌症死亡的主要原因,这是由于缺乏早期诊断标志物和特定药物。先前的研究表明 LUAD 的生长与异常的可变剪接 (AS) 有关。本文从癌症基因组图谱 (TCGA) 数据库中提取了 535 个肿瘤组织和 59 个正常组织的临床数据。使用 ESTIMATE 算法分析每个样本; 比较高评分组 (基质或免疫) 和低评分组 (基质或免疫) ,以确定总生存率和无进展生存率相关的差异表达 AS (DEAS) 事件。然后对这些 DEAS 进行非监督聚类,然后确定它们与存活率、免疫细胞和肿瘤微环境 (TME) 的关系。接下来,使用生物信息学工具开发两个预后特征来探索 LUAD 病例的预后。使用五个 OS 和六个 PFS 相关的 DEAS 事件建立预后风险评分模型。与高风险组 (HRG) 相比,低风险组 (LRG) 的 PFS 和 OS 相当可观。此外,预后较好与患者 ESTIMATE 评分以及免疫细胞浸润密切相关。我们对 LUAD 中 AS 事件的分析不仅有助于阐明 AS 的肿瘤发生机制,而且为揭示潜在的预后生物标志物和治疗靶点提供了思路。