Department of Interventional Medicine, Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Shinan District, Qingdao, Shandong Province, China.
Department of Medical Imaging, Qingdao Women and Children's Hospital, 6 Tongfu Road, Shibei District, Qingdao, Shandong, China.
Comput Math Methods Med. 2022 Apr 29;2022:2807354. doi: 10.1155/2022/2807354. eCollection 2022.
Long noncoding RNAs (lncRNAs) are becoming a critical class of metabolic regulate molecule in cancer. Glutamine is a regulator that contributes to each of the core metabolic tasks in proliferating tumor cells. Thus, we aimed to evaluate the association of lncRNAs with glutamine metabolism in lung adenocarcinoma (LUAD).
Using single-sample gene set enrichment analysis (ssGSEA), LUAD specimens were assigned scores based on glutamine metabolism-related genes, and the shared common glutamine metabolism-related lncRNAs in three different LUAD data cohorts were identified. ConsensusClusterPlus was used to perform unsupervised clustering analysis in patients with LUAD. Key glutamine metabolism-related lncRNAs were identified by first-order partial correlation analysis.
A total of 11 shared glutamine metabolism-associated lncRNAs were identified in three LUAD data cohorts, and LUAD patients were classified into three glutamine metabolism subtypes based on the expressions of the related genes. C1 exhibited shorter overall survival (OS), poor genomic instability, and inadequate infiltration of immune cell types in the tumor microenvironment (TME) and was representative of the immunodeficiency phenotype. C2 represented the immunosuppressive phenotype while C3 represented the immune activation phenotype, exhibiting the highest sensitivity to immunotherapy. Nine of the 11 lncRNAs were localized to the nucleus. Finally, three key lncRNAs, significantly enriched in multiple metabolic pathways, were screened and found to be remarkably related to the OS of LUAD.
We identified three glutamine metabolism subtypes of LUAD, which reflected different OS, genomic, and TME features, and identified three key glutamine metabolism-associated lncRNAs may contribute to further study of lncRNAs in cancer metabolism.
长链非编码 RNA（lncRNA）正在成为癌症中代谢调控分子的一个重要类别。谷氨酰胺是一种调节剂，有助于增殖肿瘤细胞的每一个核心代谢任务。因此，我们旨在评估 lncRNA 与肺腺癌（LUAD）中谷氨酰胺代谢的相关性。
使用单样本基因集富集分析（ssGSEA），根据与谷氨酰胺代谢相关的基因对 LUAD 标本进行评分，并确定了三个不同的 LUAD 数据队列中共同存在的与谷氨酰胺代谢相关的 lncRNA。使用 ConsensusClusterPlus 对 LUAD 患者进行无监督聚类分析。首先通过一阶偏相关分析确定关键的谷氨酰胺代谢相关 lncRNA。
在三个 LUAD 数据队列中共鉴定出 11 个共同的谷氨酰胺代谢相关 lncRNA，根据相关基因的表达，将 LUAD 患者分为三种谷氨酰胺代谢亚型。C1 表现出较短的总生存期（OS）、较差的基因组不稳定性和肿瘤微环境（TME）中免疫细胞类型的不足浸润，代表免疫缺陷表型。C2 代表免疫抑制表型，而 C3 代表免疫激活表型，对免疫治疗的敏感性最高。这 11 个 lncRNA 中有 9 个定位于核内。最后，筛选出三个关键的 lncRNA，它们显著富集在多个代谢途径中，与 LUAD 的 OS 显著相关。
我们鉴定了三种 LUAD 的谷氨酰胺代谢亚型，反映了不同的 OS、基因组和 TME 特征，并确定了三个关键的谷氨酰胺代谢相关 lncRNA 可能有助于进一步研究癌症代谢中的 lncRNA。
