Zhao Ye, Feng Hai-Ming, Yan Wei-Jian, Qin Yu
First Clinical Medical College, Lanzhou University, Lanzhou, China.
Department of Thoracic Surgery, The Second Affiliated Hospital of Lanzhou University, Lanzhou, China.
Front Med (Lausanne). 2022 Feb 21;9:833829. doi: 10.3389/fmed.2022.833829. eCollection 2022.
Reactive Oxygen Species (ROS) are present in excess amounts in patients with tumors, and these ROS can kill and destroy tumor cells. Therefore, tumor cells upregulate ROS-related genes to protect them and reduce their destructing effects. Cancer cells already damaged by ROS can be repaired by expressing DNA repair genes consequently promoting their proliferation. The present study aimed to identify the signature genes of and regulating network of ROS-related genes and DNA repair genes in lung adenocarcinoma (LUAD) using transcriptomic data of public databases. The LUAD transcriptome data in the TCGA database and gene expressions from Gene Expression Omnibus (GEO) were analyzed and samples were clustered into 5 ROS-related categories and 6 DNA repair categories. Survival analysis revealed a significant difference in patient survival between the two classification methods. In addition, the samples corresponding to the two categories overlap, thus, the gene expression profile of the same sample with different categories and survival prognosis was further explored, and the connection between ROS-related and DNA repair genes was investigated. The interactive sample recombination classification was used, revealing that the patient's prognosis was worse when the ROS-related and DNA repair genes were expressed at the same time. The further research on the potential regulatory network of the two categories of genes and the correlation analysis revealed that ROS-related genes and DNA repair genes have a mutual regulatory relationship. The ROS-related genes namely NQO1, TXNRD1, and PRDX4 could establish links with other DNA repair genes through the DNA repair gene NEIL3, thereby balancing the level of ROS. Therefore, targeting ROS-related genes and DNA repair genes might be a promising strategy in the treatment of LUAD. Finally, a survival prognostic model of ROS-related genes and DNA repair genes was established (TERT, PRKDC, PTTG1, SMUG1, TXNRD1, CAT, H2AFX, and PFKP). The risk score obtained from our survival prognostic model could be used as an independent prognostic factor in LUAD patients.
活性氧（ROS）在肿瘤患者体内过量存在，这些ROS能够杀死并破坏肿瘤细胞。因此，肿瘤细胞上调ROS相关基因以保护自身并降低其破坏作用。已被ROS损伤的癌细胞可通过表达DNA修复基因进行修复，从而促进其增殖。本研究旨在利用公共数据库的转录组数据，鉴定肺腺癌（LUAD）中ROS相关基因和DNA修复基因的特征基因及调控网络。分析了TCGA数据库中的LUAD转录组数据以及基因表达综合数据库（GEO）中的基因表达情况，并将样本聚类为5个ROS相关类别和6个DNA修复类别。生存分析显示，两种分类方法在患者生存方面存在显著差异。此外，这两类别的样本存在重叠，因此，进一步探究了同一样本在不同类别下的基因表达谱及其生存预后，并研究了ROS相关基因与DNA修复基因之间的联系。采用交互式样本重组分类法，结果显示当ROS相关基因和DNA修复基因同时表达时，患者预后较差。对这两类基因潜在调控网络的进一步研究及相关性分析表明，ROS相关基因与DNA修复基因存在相互调控关系。ROS相关基因NQO1、TXNRD1和PRDX4可通过DNA修复基因NEIL3与其他DNA修复基因建立联系，从而平衡ROS水平。因此，靶向ROS相关基因和DNA修复基因可能是治疗LUAD的一种有前景的策略。最后，建立了ROS相关基因和DNA修复基因的生存预后模型（TERT、PRKDC、PTTG1、SMUG1、TXNRD1、CAT、H2AFX和PFKP）。我们的生存预后模型获得的风险评分可作为LUAD患者的独立预后因素。
