基于生物信息学分析核苷酸结合寡聚化结构域样受体蛋白6在肝癌预后中的作用

摘要/Abstract

摘要： 目的：通过生物信息学分析Nod样受体pyrin结构域蛋白6（Nod-like receptor pyrin domain-containing protein 6,NLRP6）在肝细胞癌（hepatocellular carcinoma,HCC）中的表达模式、生物学功能和免疫细胞浸润关系。
方法：利用癌症和肿瘤基因图谱（the cancer genome atlas,TCGA）、国际肿瘤基因组协作组（International Cancer Genome Consortium,ICGC）、基因表达综合（gene expression omnibus,GEO）数据库及TIMER 2.0数据库、HCCDB数据库、人类蛋白质图谱（The Human Protein Atlas,HPA）数据库、基因表达谱交互分析（Gene Expression Profiling Interactive Analysis,GEPIA）数据库分析NLRP6在HCC中的表达模式、临床预后价值。通过Enrichr数据库分析NLRP6的生物学功能。分析NLRP6表达与HCC免疫细胞浸润关系。此外,基于NLRP6表达构建Nomogram模型预测HCC患者预后。
结果：NLRP6表达在多种类型肿瘤（包括HCC）中下调（P<0.05）,其低表达与HCC不良预后相关（P<0.05）。京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes,EGGK）信号通路和基因本体论（gene ontology,GO）分析结果揭示,NLRP6参与炎症-免疫调节反应,包括原发性免疫缺陷、自然杀伤细胞介导的细胞毒性、Th1和Th2细胞分化等信号通路。NLRP6表达与B细胞（r=-0.202）、CD4⁺T细胞（r=-0.207）、CD8⁺ T细胞（r=0.153）、中性粒细胞（r=0.201）、巨噬细胞（r=-0.133）和髓树突状细胞（r=-0.245）浸润丰度显著相关;高中性粒细胞浸润丰度与HCC患者更差生存预后相关（P<0.05）。基于NLRP6表达、年龄和TNM分期的Nomogram模型能有效预测HCC患者1年、3年及5年总生存率,提供显著临床净收益。
结论：NLRP6可能参与HCC发病机制,与炎症-免疫调节及免疫细胞浸润相关。基于NLRP6表达的Nomogram模型能有效预测HCC患者预后,为临床医师治疗HCC提供新的思路。

关键词: Nod样受体pyrin结构域蛋白6, 肝细胞癌, 预后, 免疫细胞浸润

Abstract: Objective:To analyze the expression pattern, biological function and immune cell infiltration relationship of Nod-like receptor pyrin domain-containing protein 6 (NLRP6) in hepatocellular carcinoma (HCC) were analyzed by bioinformatics.
Method:Multiple public databases were used to analyze the expression pattern and clinical prognostic value of NLRP6 in HCC. The biological function of NLRP6 was analyzed by the Enrichr database. The relationship between NLRP6 expression and HCC immune cell infiltration was analyzed. In addition, a Nomogram model was constructed based on NLRP6 to predict the prognosis of HCC patients.
Result:NLRP6 expression was down-regulated in various cancer types (including HCC) (P<0.05), and its low expression was associated with poor prognosis in HCC (P<0.05). Resultsof Kyoto Encyclopedia of Genes and Genomes (EGGK) signaling pathway and gene ontology (GO) analysis reveal that NLRP6 is involved in inflammatory-immunomodulatory responses, including primary immunodeficiency, natural killer cell-mediated cytotoxicity, and Th1 and Th2 cell differentiation signal pathway. NLRP6 expression was correlated with B cells (r=-0.202), CD⁴⁺ T cells (r=-0.207), CD⁸⁺ T cells (r=0.153), neutrophils (r=-0.201), macrophages (r=-0.133 ) and myeloid dendritic cells (r=-0.245) infiltration abundance were significantly correlated and high neutrophil infiltration abundance was associated with worse survival prognosis in HCC patients (P<0.05). The Nomogram model based on NLRP6, age and TNM stage can effectively predict the 1 year, 3 years and 5 years overall survival rates of HCC patients, providing a significant clinical net benefit.
Conclusion:NLRP6 may be involved in the pathogenesis of HCC and is associated with inflammation-immune regulation and immune cell infiltration. The Nomogram model based on NLRP6 can effectively predict the prognosis of HCC patients and provide new ideas for clinicians to treat HCC.

Key words: Nod-like receptor pyrin domain-containing protein 6, Hepatocellular carcinoma, Prognosis, Immune infiltration

黄迪, 武雪亮, 李飞, 韩山山, 高鑫. 基于生物信息学分析核苷酸结合寡聚化结构域样受体蛋白6在肝癌预后中的作用[J]. 肝癌电子杂志, 2022, 9(2): 13-22.

Huang Di, Wu Xueliang, Li Fei, Han Shanshan, Gao Xin. The role of nucleotide binding oligomerization domain like receptor protein 6 in the prognosis of hepatocellular carcinoma based on bioinformatics analysis[J]. Electronic Journal of Liver Tumor, 2022, 9(2): 13-22.

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