Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450008, China.
Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai 200032, China.
Aging (Albany NY). 2020 May 23;12(10):9868-9881. doi: 10.18632/aging.103251.
Long non-coding RNAs (lncRNAs) play an important role in various biological processes of lung adenocarcinoma (LUAD), such as immune response regulation, tumor microenvironment remodeling and genomic alteration. Nevertheless, immune-related lncRNAs and their immune and genomic alterations characteristics in LUAD samples still remain unreported. Here, using various public databases, statistic and software tools, we constructed two immune-related lncRNA clusters with different immune and genomic alterations characteristics. Notably, cluster 1 had a stronger immunosuppressive tumor microenvironment (TME) and a higher mutation frequency than cluster 2, especially the mutant genes, such as Kelch-like ECH-associated protein 1 (KEAP1) and toll like receptor 4 (TLR4). In cluster 1, both the amplified and deleted portions of copy number variation (CNV) segments were enriched and cyclin dependent kinase inhibitor 2A (CDKN2A) was significantly deleted. GSVA analysis revealed that these immune-related lncRNAs may be involved in stem cell and EMT functions. Furthermore, cluster 1 was related to worse prognosis of LUAD patients. Therefore, we constructed two immune-related and prognostic lncRNA clusters and identified their immune and genomic alterations characteristics in LUAD samples, which could well divide LUAD patients into different immune phenotypes and help to understand immune molecular mechanisms of LUAD.
长链非编码 RNA（lncRNAs）在肺腺癌（LUAD）的各种生物学过程中发挥重要作用，例如免疫反应调节、肿瘤微环境重塑和基因组改变。然而，LUAD 样本中的免疫相关 lncRNA 及其免疫和基因组改变特征仍然尚未报道。在这里，我们使用各种公共数据库、统计和软件工具，构建了两个具有不同免疫和基因组改变特征的免疫相关 lncRNA 簇。值得注意的是，簇 1 具有更强的免疫抑制性肿瘤微环境（TME）和比簇 2更高的突变频率，特别是突变基因，如 Kelch-like ECH-associated protein 1（KEAP1）和 toll like receptor 4（TLR4）。在簇 1 中，拷贝数变异（CNV）片段的扩增和缺失部分均被富集，并且 cyclin dependent kinase inhibitor 2A（CDKN2A）显著缺失。GSVA 分析表明，这些免疫相关 lncRNA 可能参与干细胞和 EMT 功能。此外，簇 1 与 LUAD 患者的预后较差相关。因此，我们构建了两个免疫相关且与预后相关的 lncRNA 簇，并鉴定了 LUAD 样本中它们的免疫和基因组改变特征，这可以将 LUAD 患者很好地分为不同的免疫表型，并有助于理解 LUAD 的免疫分子机制。
