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Nanopore测序揭示m6A修饰铁死亡相关基因在中晚期头颈部鳞状细胞癌中的表达及临床意义
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福建省自然科学基金项目（2020J011281）。


Expressions and clinical significances of m6A-modified iron death-related genes in middle and advanced head and neck squamous cell carcinoma
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    摘要:

    目的 研究N6-甲基腺苷（m6A）修饰在中晚期头颈部鳞状细胞癌（HNSCC）的作用和基因相关通路，为头颈部HNSCC患者的个体化精准治疗提出新的观点及研究参考。方法 选取3对临床中晚期HNSCC患者的癌及其癌旁组织（6个样本）进行测序，从癌和癌旁组织的转录组、m6A相关差异基因中筛选出两者共同的差异基因，通过基因本体（GO）分析、pathway分析及蛋白相互作用（PPI）分析，找出其中的枢纽（hub）基因，随后对网络中的基因进行基因集变异分析（GSVA），从而得到m6A修饰影响的基因及通路。结果 从癌与癌旁组织的差异基因中筛选出96个转录组m6A相关的上调基因、159个m6A相关下调基因；信号通路分析发现PPAR通路、免疫相关通路下调，代谢通路上调；构建PPI后发现，CDK1呈现上调趋势，而DCN及ARG2均呈现下调趋势；GSVA分析发现PI3K/AKT信号通路在癌组织中上调；PPI中的hub基因共表达分析发现AGR2和CDK1在m6A调控下，与铁死亡相关基因联系很密切。结论 m6A修饰与FOXA1、RPL8、DNC、CDK1、ApoE、POSTN、YWHAZ、MMP13等铁死亡相关基因紧密相关，m6A修饰可能通过铁死亡相关基因影响免疫、代谢相关通路，从而在中晚期HNSCC中起重要作用。

    Abstract:

    Objective To study the role and gene-related pathways of N6-methyladenosine (m6A) modification in middle and advanced head and neck squamous cell carcinoma (HNSCC), and to propose new perspectives and research references for individualized and precise treatment of HNSCC patients.Methods Cancer and paracancerous tissues (6 samples) from 3 middle and advanced HNSCC patients were selected for sequencing, and the transcriptomes and m6A-related differential genes from the cancer and paracancerous tissues were screened to identify common differential genes shared by both, and the hub genes were identified through gene ontology (GO) analysis, pathway analysis, and protein-protein interaction (PPI) analysis, and then the network of the genes in the network were subsequently subjected to gene set variation analysis (GSVA) to obtain the genes and pathways affected by m6A modification.Results From the differential genes of cancer and paracancer tissues, 96 m6A-related up-regulated genes and 159 m6A-related down-regulated genes were screened out from the transcriptome. Signaling pathway analysis revealed that peroxisome proliferator-activated receptor (PPAR) pathway, immune-related pathway were down-regulated, and metabolic pathway was up-regulated. After constructing the PPI, the cell-cycle protein-dependent kinase 1 (CDK1) was up-regulated, and the decorin (DCN) and anterior gradient 2 (ARG2) were down-regulated. Gene set variation analysis (GSVA) revealed that the PI3K/AKT signaling pathway was up-regulated in cancer tissues. Coexpression analysis of hub genes in the PPIs revealed that AGR2 and CDK1 were very closely linked to iron death-related genes under the regulation of m6A.Conclusions m6A modification is closely associated with iron death-related genes such as FOXA1, ribosomal protein L8(RPL8), DNC, CDK1, apolipoprotein E(ApoE), Periostin (POSTN), YWHAZ, Matrix metalloproteinase-13(MMP13), etc. m6A modification may affect immune and metabolism-related pathways through iron death-related genes, and thus play an important role in middle and advanced HNSCC.

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庄黎明,丁雅婷,蔡成福,叶辉,蔡耿明. Nanopore测序揭示m6A修饰铁死亡相关基因在中晚期头颈部鳞状细胞癌中的表达及临床意义[J].中国耳鼻咽喉颅底外科杂志,2023,29(5):60-70

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  • 收稿日期:2023-06-17
  • 在线发布日期: 2023-10-31

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