目的:了解同源异型盒(HOX)和突变基因在头颈癌进展中的调节作用至关重要,尽管他们的互动仍然难以捉摸。这项研究旨在破译突变驱动效应对同源异型盒基因的关键调控,以增强我们对头颈部癌症进展的理解。
方法:使用用于体细胞变异检测的VarScan2分析来自癌症基因组图谱-头颈部鳞状细胞癌的基因组突变数据。突变聚类,驱动突变识别,和癌症信号通路分析使用OncodriveCLUST方法进行。检索协调组数据集以鉴定影响HOX基因的关键癌症驱动基因。使用癌病毒数据库评估HPV感染对HOX和突变基因的影响。用基因集癌症分析分析了由于癌症驱动因素对HOX基因的影响而改变的途径活性。使用ClusterProfilerR包进行基因本体论生物过程和分子功能的功能富集分析。
结果:在具有突变TP53、FAT1和CDKN2A的头颈部癌组中观察到HOX基因的显著改变。HOX基因被鉴定为TP53的功能下游靶标,表示转录介导的调控。HOX基因与突变的TP53,FAT1和CDKN2A之间的相互作用失调了上皮-间质转化,细胞周期,和凋亡途径在头颈部癌症进展。
结论:癌症驱动基因和HOX基因之间的相互作用在调节头颈部鳞状细胞癌发病机制的致癌过程中至关重要。
OBJECTIVE: Understanding the regulatory role of homeobox (
HOX) and mutated genes in the progression of head and neck cancers is essential, although their interaction remains elusive. This study aims to decipher the critical regulation of mutation driven effects on homeobox genes to enhance our understanding of head and neck cancer progression.
METHODS: Genomic mutation data from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma were analyzed using VarScan2 for somatic variant detection. Mutational clustering, driver mutation identification, and cancer signaling pathway analysis were performed using the OncodriveCLUST method. Harmonizome datasets were retrieved to identify critical cancer driver genes affecting
HOX genes. The effects of HPV infection on
HOX and mutated genes were assessed using the oncoviral database. Altered pathway activity due to the effects of cancer drivers on
HOX genes was analyzed with Gene Set Cancer Analysis. Functional enrichment analysis of gene ontology biological processes and molecular functions was conducted using the ClusterProfiler R package.
RESULTS: Significant alterations in
HOX genes were observed in head and neck cancer cohorts with mutated TP53, FAT1, and CDKN2A. HOX genes were identified as functionally downstream targets of TP53, signifying transcriptionally mediated regulation. The interaction between HOX genes and mutated TP53, FAT1, and CDKN2A dysregulated the epithelial-to-mesenchymal transition, cell cycle, and apoptosis pathways in head and neck cancer progression.
CONCLUSIONS: The interplay between cancer driver genes and HOX genes is pivotal in regulating the oncogenic processes underlying the pathogenesis of head and neck squamous cell carcinoma.