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解析ZEB2基因网络中的基因改变及其与头颈部鳞状细胞癌(HNSCC)的可能关联。

Deciphering the Genetic Alteration in the ZEB2 Gene Network and Their Possible Association With Head and Neck Squamous Cell Carcinoma (HNSCC).

作者信息

S Dhivya, P Anitha, As Smiline Girija, A Paramasivam, J Vijayashree Priyadharsini

机构信息

Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND.

Clinical Genetics Lab, Centre for Cellular and Molecular Research, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND.

出版信息

Cureus. 2023 Oct 3;15(10):e46440. doi: 10.7759/cureus.46440. eCollection 2023 Oct.

Abstract

Background Head and neck squamous cell carcinoma (HNSCC) is an abnormal growth of cells that leads to tumor formation in the head and neck region. Several genes and genetic networks are involved in the process of carcinogenesis. Aim The aim of the present study is to unravel the prognostic marker from a pool of interacting networks governed by the ZEB2gene Materials and methods Computational analysis was employed to identify the protein network interactions, genetic alterations, gene expression, and the survival analysis of the ZEB2 dysregulated network in the head and neck cancer dataset (HNSCC) from the Cancer Genome Atlas (TCGA), Firehose Legacy. The gene expression profiling and survival analysis were performed for the gene with the highest frequency of genetic alteration. Result The interaction network returned nine genes that interact with ZEB2. The ARHGAP31 gene was found to harbor the highest frequency of alteration at the genomic as well as the transcriptomic levels. Survival was also found to be significant with respect to the differential gene expression pattern while comparing the genders and different ethnic groups. Females with higher expression of ARHGAP31 and the Asian population exhibiting low/medium expression of the same were found to present with poor survival probability. Conclusion The identification of putative drivers or a candidate gene of a network could provide clues about the association with the disease phenotype of HNSCC. The present study identifies ARHGAP31 as the key gene of the ZEB2 gene network, wherein the genetic alterations correlate with the transcriptomics data and the survival probability of patients segregated based on gender and race. Further experimental evaluation is warranted to confirm the association of this infamous gene ARHGAP31 with the development of oral carcinoma.

摘要

背景

头颈部鳞状细胞癌(HNSCC)是一种细胞异常生长,导致头颈部区域形成肿瘤。几个基因和基因网络参与了致癌过程。

目的

本研究的目的是从由ZEB2基因控制的相互作用网络中找出预后标志物。

材料和方法

采用计算分析来识别来自癌症基因组图谱(TCGA)Firehose Legacy的头颈部癌数据集(HNSCC)中ZEB2失调网络的蛋白质网络相互作用、基因改变、基因表达和生存分析。对基因改变频率最高的基因进行基因表达谱分析和生存分析。

结果

相互作用网络返回了9个与ZEB2相互作用的基因。发现ARHGAP31基因在基因组和转录组水平上具有最高的改变频率。在比较性别和不同种族群体时,差异基因表达模式的生存情况也具有显著性。发现ARHGAP31高表达的女性和该基因低/中度表达的亚洲人群生存概率较差。

结论

确定网络中的假定驱动因素或候选基因可以为与HNSCC疾病表型的关联提供线索。本研究确定ARHGAP31是ZEB2基因网络的关键基因,其中基因改变与转录组学数据以及根据性别和种族划分的患者生存概率相关。需要进一步的实验评估来证实这个声名狼藉的基因ARHGAP31与口腔癌发生的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/944c/10622604/a10ae6fc9a6a/cureus-0015-00000046440-i01.jpg

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