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基于全面基因信息的系统生物学方法预测肺癌相关基因。

Prediction of Genes Involved in Lung Cancer with a Systems Biology Approach Based on Comprehensive Gene Information.

机构信息

Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Systems Biomedicine Unit, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Biochem Genet. 2022 Aug;60(4):1253-1273. doi: 10.1007/s10528-021-10163-7. Epub 2021 Dec 2.

Abstract

Over the past few years, hundreds of genes have been reported in relation to lung cancer. Systems biology studies can help validate this association and find the most valid genes to use in the diagnosis and treatment. We reviewed the candidate genes for lung cancer in 120 published articles from September 1, 1993, to September 1, 2020. We obtained 134 up- and 36 downregulated genes for lung cancer in this article. The genes extracted from the articles were imported to Search Tool for the Retrieval of Interacting genes/proteins (STRING) to construct the protein-protein interaction (PPI) Network and pathway enrichment. GO ontology and Reactome databases were used for describing the genes, average length of survival, and constructing networks. Then, the ClusterONE plugin of Cytoscape software was used to analyze and cluster networks. Hubs and bottleneck nodes were defined based on their degree and betweenness. Common genes between the ClusterONE plugin and network analysis consisted of seven genes (BRCA1-TP53-CASP3-PLK1-VEGFA-MDM2-CCNB1 and PLK1), and two genes (PLK1 and TYMS) were selected as survival factors. Our drug-gene network showed that CASP3, BRCA1, TP53, VEGFA, and MDM2 are common genes that are involved in this network. Also, among the drugs recognized in the drug-gene network, five drugs such as paclitaxel, oxaliplatin, carboplatin, irinotecan, and cisplatin were examined in different studies. It seems that these seven genes, with further studies and confirmatory tests, could be potential markers for lung cancer, especially PLK1 that has a significant effect on the survival of patients. We provide the novel genes into the pathogenesis of lung cancer, and we introduced new potential biomarkers for this malignancy.

摘要

在过去的几年中,已经有数百个与肺癌相关的基因被报道。系统生物学研究可以帮助验证这种关联,并找到最有效的基因用于诊断和治疗。我们回顾了 1993 年 9 月 1 日至 2020 年 9 月 1 日期间发表的 120 篇文章中有关肺癌的候选基因。本文获得了肺癌的 134 个上调基因和 36 个下调基因。从文章中提取的基因被导入到 Search Tool for the Retrieval of Interacting genes/proteins(STRING)中,以构建蛋白质-蛋白质相互作用(PPI)网络和通路富集。GO 本体和 Reactome 数据库用于描述基因、平均生存长度和构建网络。然后,使用 Cytoscape 软件的 ClusterONE 插件分析和聚类网络。根据其度和介数定义了枢纽和瓶颈节点。ClusterONE 插件和网络分析之间的共同基因包括七个基因(BRCA1-TP53-CASP3-PLK1-VEGFA-MDM2-CCNB1 和 PLK1),并且选择了两个基因(PLK1 和 TYMS)作为生存因子。我们的药物-基因网络显示,CASP3、BRCA1、TP53、VEGFA 和 MDM2 是共同涉及该网络的基因。此外,在药物-基因网络中识别的药物中,五种药物,如紫杉醇、奥沙利铂、卡铂、伊立替康和顺铂,在不同的研究中进行了检查。似乎这七个基因,通过进一步的研究和验证测试,可能成为肺癌的潜在标志物,特别是 PLK1,它对患者的生存有显著影响。我们为肺癌的发病机制提供了新的基因,并为这种恶性肿瘤引入了新的潜在生物标志物。

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