Abstract
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.
Highlights
Reactive oxygen species (ROS) are small oxygen-derived active small molecules, including O2·,·OH, RO2·, and RO·(1)
The ROS-related gene set as the hallmark of ROS-related pathway containing 49 genes, and the DNA repair gene set Kauffmann DNA repair genes [1] containing 230 DNA repair genes were downloaded from the Molecular Signatures Database (MSigDB) and used with the Gene Set Enrichment Analysis (GSEA)
The intersection of these genes with the genes from the Cancer Genome Atlas (TCGA) resulted in a total of 45 ROS-related genes and 194 DNA repair genes
Summary
Reactive oxygen species (ROS) are small oxygen-derived active small molecules, including O2·-,·OH, RO2·, and RO·(1). The increase of the level of intracellular ROS can allow the selective killing of tumor cells [2]. The expression of ROS-related proteins increases in many types of cancer, and they are involved in cell growth, proliferation, differentiation, protein synthesis, glucose metabolism, cell survival and inflammation [4]. The presence of oxidative stress greatly increases gene damage, and the damage to the mitochondrial DNA of alveolar cells can cause energy supply barriers, promote tumor blood vessel formation, and inhibit tumor immune microenvironment. These multiple effects promote the occurrence of NSCLC. NSCLC cells maintain the oxidative stress response at the appropriate level for their proliferation and survival by regulating their antioxidant levels and ROS levels [10, 11]
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