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抗氧化基因突变的虚拟筛选及其与头颈癌的潜在关联:一种计算机方法。

Virtual screening of mutations in antioxidant genes and its putative association with HNSCC: An in silico approach.

机构信息

Biomedical Research Unit and Laboratory Animal Centre (BRULAC) - Dental Research Cell (DRC), Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Poonamallee High Road, Chennai 600 077, Tamil Nadu, India.

Biomedical Research Unit and Laboratory Animal Centre (BRULAC) - Dental Research Cell (DRC), Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Poonamallee High Road, Chennai 600 077, Tamil Nadu, India.

出版信息

Mutat Res. 2020 May-Dec;821:111710. doi: 10.1016/j.mrfmmm.2020.111710. Epub 2020 Jun 9.

Abstract

Abnormalities in the antioxidant pathway are usually associated with inflammatory conditions, followed by tissue damage. Cancer is one such disease where there is a build-up of reactive oxygen species leading to pathological consequences. The present study aims to identify the alteration in genes and proteins associated with the common antioxidant pathways among patients with head and neck squamous cell carcinoma (HNSCC). The study design follows a retrospective approach and employs computational tools to analyse the possible role of genes involved in the anti-oxidation pathways in patients with HNSCC. The TCGA PanCancer Atlas dataset was used for the analysis. The Oncoprint data were analysed further to obtain information on the type of gene alterations encountered in the HNSCC cases. Gene amplification and deletions were commonly observed in genes of the thiol reductase pathway, whereas substitutions leading to missense, frameshifts were found in the other pathways assessed. Gene encoding ceruloplasmin was found to harbor nucleotide variations in about 10 % of the patients with OSCC. An exhaustive knowledge of the molecular genetic mechanisms underlying the pathways identified can open new avenues in selecting candidate genes which can be used as therapeutic targets against HNSCC. The present work identifies and nominates crucial genes from the antioxidant system for further in vitro experiments.

摘要

抗氧化途径的异常通常与炎症状态有关,随后是组织损伤。癌症就是这样一种疾病,其中活性氧物质的积累导致病理后果。本研究旨在确定与头颈鳞状细胞癌 (HNSCC) 患者常见抗氧化途径相关的基因和蛋白质的变化。该研究设计采用回顾性方法,并使用计算工具分析参与抗氧化途径的基因在 HNSCC 患者中的可能作用。使用 TCGA PanCancer Atlas 数据集进行分析。进一步分析 Oncoprint 数据以获取 HNSCC 病例中遇到的基因改变类型的信息。巯基还原酶途径的基因扩增和缺失很常见,而在评估的其他途径中则发现了导致错义、移码的取代。约 10%的口腔鳞状细胞癌患者的铜蓝蛋白基因编码存在核苷酸变异。对确定的途径的分子遗传机制有详尽的了解,可以为选择候选基因开辟新途径,候选基因可用作针对 HNSCC 的治疗靶点。本工作从抗氧化系统中鉴定和提名关键基因,以进行进一步的体外实验。

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