Department of Respiratory Medicine, The Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Yiwu 322000, China.
Department of Cardiothoracic Surgery, The Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Yiwu 322000, China.
Genes (Basel). 2022 Jan 27;13(2):238. doi: 10.3390/genes13020238.
Lung adenocarcinoma (LUAD) is often diagnosed at an advanced stage, so it is necessary to identify potential biomarkers for the early diagnosis and prognosis of LUAD. In our study, a gene co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) in order to obtain the key modules and genes correlated with LUAD prognosis. Four hub genes (HLF, CHRDL1, SELENBP1, and TMEM163) were screened out using least absolute shrinkage and selection operator (LASSO)-Cox regression analysis; then, a prognostic model was established for predicting overall survival (OS) based on these four hub genes..Furthermore, the prognostic values of this four-gene signature were verified in four validation sets (GSE26939, GSE31210, GSE72094, and TCGA-LUAD) as well as in the GEPIA database. To assess the prognostic values of hub genes, receiver operating characteristic (ROC) curves were constructed and a nomogram was created. We found that a higher expression of four hub genes was associated with a lower risk of patient death. In a training set, it was demonstrated that this four-gene signature was a better prognostic factor than clinical factors such as age and stage of disease. Moreover, our results revealed that these four genes were suppressor factors of LUAD and that their high expression was associated with a lower risk of death. In summary, we demonstrated that this four-gene signature could be a potential prognostic factor for LUAD patients. These findings provide a theoretical basis for exploring potential biomarkers for LUAD prognosis prediction in the future.
肺腺癌(LUAD)通常在晚期诊断,因此有必要确定 LUAD 的早期诊断和预后的潜在生物标志物。在我们的研究中,使用加权基因共表达网络分析(WGCNA)构建了基因共表达网络,以获得与 LUAD 预后相关的关键模块和基因。使用最小绝对值收缩和选择算子(LASSO)-Cox 回归分析筛选出四个枢纽基因(HLF、CHRDL1、SELENBP1 和 TMEM163);然后,基于这四个枢纽基因建立了预测总生存期(OS)的预后模型。此外,还在四个验证集(GSE26939、GSE31210、GSE72094 和 TCGA-LUAD)和 GEPIA 数据库中验证了这四个基因特征的预后价值。为了评估枢纽基因的预后价值,构建了接收器操作特征(ROC)曲线并创建了列线图。我们发现,四个枢纽基因的高表达与患者死亡风险降低相关。在训练集中,证明该四个基因特征比年龄和疾病阶段等临床因素更能作为更好的预后因素。此外,我们的结果表明,这四个基因是 LUAD 的抑制因子,其高表达与死亡风险降低相关。总之,我们证明了该四个基因特征可以成为 LUAD 患者的潜在预后因素。这些发现为未来探索 LUAD 预后预测的潜在生物标志物提供了理论依据。