Li Na, Su Mu, Zhu Louyin, Wang Li, Peng Yonggang, Dong Bo, Ma Liya, Liu Yongyu
Department of Central Laboratory, Shenyang Tenth People's Hospital, Shenyang Chest Hospital, Shenyang, Liaoning, People's Republic of China.
Berry Oncology Corporation, Beijing, People's Republic of China.
Int J Gen Med. 2021 Nov 27;14:8955-8974. doi: 10.2147/IJGM.S340615. eCollection 2021.
Long noncoding RNAs (lncRNAs) and glycolysis regulate multiple types of cancer. However, the prognostic roles and biological functions of glycolysis-related lncRNAs in lung adenocarcinoma (LUAD) remain unclear. In this study, we investigated the role of glycolysis-related lncRNAs in LUAD.
We retrieved glycolysis-related genes from the Molecular Signatures Database and screened for prognostic glycolysis-related lncRNAs from The Cancer Genome Atlas.
We identified three LUAD subtypes (clusters 1-3) by univariate Cox regression analysis and consensus clustering. Patients in cluster 1 had the best overall survival rates. Immune, stromal, and cytolytic-activity scores were the highest in cluster 1. The expression of immune checkpoint molecules (programmed cell death protein 1 and cytotoxic T-lymphocyte-associated protein 4) and other immune-related indicators was the highest in cluster 1, whereas that of epithelial cell biomarkers (Cadherin 1, Cadherin 2, and MET) was the lowest. Therefore, patients in cluster 1 may benefit from immunotherapy. Lasso-Cox regression and multivariate Cox regression analyses were used to select nine lncRNAs to build a robust prognostic model of LUAD. The area under the curve classifier values and a nomogram performed well in predicting survival times for patients with LUAD. The expression levels of nine lncRNAs were validated by quantitative reverse transcriptase-polymerase chain reaction analysis, and most of these lncRNAs were significantly related to immune-related mRNAs. Gene set enrichment analysis revealed that the high-risk group was enriched for cell cycle-related pathways and the low-risk group was enriched for pathways associated with immunity or immune-related diseases.
The LUAD subtypes and prognostic model developed here may help in clinical risk stratification, prognosis management, and treatment decisions for patients with LUAD.
长链非编码RNA（lncRNAs）和糖酵解在多种癌症中发挥调节作用。然而，糖酵解相关lncRNAs在肺腺癌（LUAD）中的预后作用和生物学功能仍不清楚。在本研究中，我们调查了糖酵解相关lncRNAs在LUAD中的作用。
我们从分子特征数据库中检索糖酵解相关基因，并从癌症基因组图谱中筛选出与预后相关的糖酵解lncRNAs。
通过单变量Cox回归分析和一致性聚类，我们鉴定出三种LUAD亚型（聚类1-3）。聚类1中的患者总生存率最佳。聚类1中的免疫、基质和细胞溶解活性评分最高。免疫检查点分子（程序性细胞死亡蛋白1和细胞毒性T淋巴细胞相关蛋白4）及其他免疫相关指标的表达在聚类1中最高，而上皮细胞生物标志物（钙黏蛋白1、钙黏蛋白2和MET）的表达在聚类1中最低。因此，聚类1中的患者可能从免疫治疗中获益。使用套索-考克斯回归和多变量考克斯回归分析选择9个lncRNAs构建一个稳健的LUAD预后模型。曲线下面积分类器值和列线图在预测LUAD患者生存时间方面表现良好。通过定量逆转录-聚合酶链反应分析验证了9个lncRNAs的表达水平，其中大多数lncRNAs与免疫相关mRNA显著相关。基因集富集分析显示，高危组富含细胞周期相关通路，低危组富含与免疫或免疫相关疾病相关的通路。
本文建立的LUAD亚型和预后模型可能有助于LUAD患者的临床风险分层、预后管理和治疗决策。
