基于生物信息学预测肝细胞癌预后基因

doi:10.6040/j.issn.1671-7554.0.2022.0128

摘要/Abstract

摘要： 目的基于生物信息学方法筛选肝癌预后基因以及探讨相关基因的作用机制。方法基于TCGA-LIHC数据集、基因表达综合(GEO)数据库、Ualcan 数据库研究了NUF2在肝癌组织和正常肝组织中的表达。采用 Wilcoxon 秩和检验分析 NUF2 表达与肝癌临床病理特征的关系,生存分析采用 Kaplan-Meier法,预后的单因素分析及多因素分析采用 Cox 比例风险回归模型。基于GO和KEGG通路富集分析探索其功能机制,利用STRING数据库进行NUF2蛋白互作网络构建,利用LinkedOmics 数据库分析NUF2的互作基因以探究NUF2在肝癌发生中的调控机制。此外,使用TIMER数据库和CIBERSORT研究NUF2的表达与肿瘤浸润性免疫细胞状态的关系。结果与正常肝组织相比,NUF2 在肝细胞癌(HCC)组织中高表达,多变量Cox回归分析确定NUF2是HCC发生的独立危险因素,NUF2高表达患者的总生存期明显短于NUF2低表达的患者。另外,通过 STRING数据库和LinkedOmics 数据库构建了 NUF2蛋白互作基因网络,功能分析显示NUF2 及其相关基因主要参与核分裂、染色体分离、有丝分裂、化学诱导的癌变、细胞周期等过程。最后,在NUF2高表达的患者中,静息记忆CD4T细胞、活化记忆CD4T细胞、滤泡辅助T细胞、调节性T细胞(Treg)和M0巨噬细胞比例较高。结论 HCC组织中NUF2表达水平的上调在HCC发生发展中起关键作用,高表达的NUF2可作为鉴别早期和晚期HCC的潜在诊断和预后标志物,提高诊断及时性和预后准确性,NUF2在HCC肿瘤发生过程中的免疫机制中起着关键作用。

关键词: NUF2, 肝细胞癌, 预后, 生物标志物, 肿瘤免疫

Abstract: Objective To screen hepatocellular carcinoma(HCC)prognostic genes based on bioinformatics methods and explore the action mechanism of related genes. Methods The expression of NUF2 in liver cancer tissues and normal liver tissues was studied based on the TCGA-LIHC dataset, the Gene Expression Omnibus(GEO)database, and the Ualcan database. The relationship of NUF2 expression and clinicopathological features of HCC was analyzed using the Wilcoxon rank-sum test. Survival analysis, univariate analysis of prognosis, and multivariate analysis were carried out using Kaplan-Meier method and Cox proportional risk regression model, respectively. The functional mechanisms was explored based on the GO and KEGG pathway enrichment analysis. NUF2 protein interaction network was constructed using the STRING database. The NUF2 interaction genes were analyzed using the LinkedOmics database to explore the regulatory mechanism of NUF2 in hepatocarcinogenesis. In addition, the relationship between NUF2 expression and tumor-infiltrating immune cell status was investigated using the TIMER database and CIBERSORT. Results Compared to normal liver tissues, NUF2 was significantly highly expressed in HCC tissues. Multivariable Cox regression analysis identified NUF2 as an independent risk factor in HCC, and patients with high NUF2 expression had significantly shorter overall survival than those with low NUF2 expression. In addition, the NUF2 protein interaction network was constructed by the STRING database and LinkedOmics database, and the functional analysis showed that NUF2 and its associated genes were mainly involved in nuclear division, chromosome segregation, mitosis, chemical-induced carcinogenesis, cell cycle and other processes. Finally, a high proportion of resting memory CD4T cells, activated memory CD4T cells, follicular helper T cells, regulatory T cells(Treg)and M0 macrophages was observed in patients with high NUF2 expression. Conclusion Upregulation of NUF2 in HCC tissues plays a key role in HCC development. High expression of NUF2 can serve as a potential diagnostic and prognostic marker to identify early and late HCC, improve timeliness and diagnostic and prognostic accuracy. NUF2 plays a key role in the immune mechanism during HCC tumorigenesis.

Key words: NUF2, Hepatocellular carcinoma, Prognosis, Biomarkers, Tumor immunity

中图分类号:

R735.7

李琳琳,王凯. 基于生物信息学预测肝细胞癌预后基因[J]. 山东大学学报 (医学版), 2022, 60(5): 50-58.

LI Linlin, WANG Kai. Prediction of hepatocellular carcinoma prognostic genes based on bioinformatics[J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 50-58.

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