Identification of Novel Neddylation-Related Molecular Subtypes in Non-Small Cell Lung Cancer With Implications for Prognosis and the Immune Landscape

IF 4.2 4区 医学 Q2 CHEMISTRY, MEDICINAL
Chuli Pan, Xiaofeng Yu
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Abstract

Lung cancer stands as the primary cause of fatalities contacted to cancer, with nonsmall cell lung cancer (NSCLC) comprising the bulk of these cases. Protein neddylation, a posttranslational alteration akin to ubiquitination. The study aims to identify neddylation-related genes in NSCLC and to predict molecular models hold significant promise for forecasting the prognosis of NSCLC patients. Clinical information stemmed from the Cancer Genome Atlas (TCGA) database; neddylation-related genes (NRGs) were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Patients were clustered into two subtypes utilizing the Kmeans method. These genes were then screened using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. A nomogram was created to predict the prognosis of NSCLC. The model was validated in independent Gene Expression Omnibus (GEO) data sets: GSE30219. We performed extensive model validations to assess the prognostic significance of the signature. The immune landscape of risk groups was characterized using Single Sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE and CIBERSORT algorithms. Subsequently, we also performed drug sensitivity evaluation. Based on the expression profiles of 26 neddylation-associated genes, we classified patients into two distinct subtypes, then identified ten neddylation-related genes that serve as prognostic biomarkers. Receiver operating characteristic (ROC) curves noted that these neddylation-related were effective in predicting patients prognosis. Furthermore, patients at high-risk have poor survival rates. Besides, high-risk group exhibited lower immune cell infiltration levels, displayed a marked divergence in the expression pattern of immune checkpoint molecules. Lastly, we identified potential drugs and evaluated the drug sensitivity for NSCLC. In conclusion, we constructed novel neddylation-related molecular subtypes and revealed their immunological characteristics that may function as prognostic biomarkers for NSCLC patients.

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鉴定非小细胞肺癌中新的类泛素化相关分子亚型及其对预后和免疫景观的影响
肺癌是与癌症接触导致死亡的主要原因,非小细胞肺癌(NSCLC)占这些病例的大部分。蛋白质类化,一种类似泛素化的翻译后改变。本研究旨在鉴定非小细胞肺癌中类化修饰相关基因,并预测分子模型对预测非小细胞肺癌患者预后具有重要意义。临床信息来源于癌症基因组图谱(TCGA)数据库;类化修饰相关基因(NRGs)从京都基因与基因组百科全书(KEGG)数据库中获得。采用Kmeans方法将患者分为两个亚型。然后使用单变量Cox回归和最小绝对收缩和选择算子(LASSO)回归对这些基因进行筛选。建立了非小细胞肺癌的nomogram预后预测图。该模型在独立的Gene Expression Omnibus (GEO)数据集GSE30219中得到验证。我们进行了广泛的模型验证,以评估签名的预后意义。使用单样本基因集富集分析(ssGSEA)、ESTIMATE和CIBERSORT算法对危险人群的免疫景观进行表征。随后,我们还进行了药物敏感性评价。基于26个类化修饰相关基因的表达谱,我们将患者分为两种不同的亚型,然后确定了10个类化修饰相关基因作为预后生物标志物。受试者工作特征(ROC)曲线显示,这些与类化相关的指标可有效预测患者预后。此外,高危患者的存活率很低。此外,高危组免疫细胞浸润水平较低,免疫检查点分子表达模式差异明显。最后,我们确定了潜在的药物并评估了NSCLC的药物敏感性。总之,我们构建了新的类化修饰相关分子亚型,并揭示了它们的免疫学特征,这些特征可能作为非小细胞肺癌患者的预后生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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