基于生物信息学NOP2在肝癌中的预后价值研究

Prognostic value of NOP2 in liver cancer based on bioinformatics

目的:基于生物信息学探究NOP2核仁蛋白(NOP2 nucleolar protein,NOP2)在肝癌预后中的价值。方法:采用CIBERSORT和ESTIMATE计算方法,计算497例(其中54例有癌旁组织)肝癌病人的肿瘤浸润免疫细胞(TICs)的两个主要评分。通过Cox回归分析寻找出差异表达基因(DEGs)。同时进一步收集蚌埠医学院第一附属医院行肝切除术的原发性肝癌病人10对癌组织及相邻癌旁组织进行qRT-PCR分析。结果:NOP2的表达水平与肝癌的病理特征(较晚的M分期)呈正相关,与病人的生存时间呈负相关。通过基因集富集分析(GSEA)发现NOP2高表达的基因主要富集于与免疫相关通路。进一步研究证实6种免疫细胞与NOP2表达呈正相关,包括M0巨噬细胞、静止期自然杀伤细胞、激活期CD4^(+)记忆T细胞、CD8^(+)T细胞、滤泡辅助性T细胞、调节性T细胞。5种免疫细胞与NOP2的表达水平呈负相关,包括记忆B细胞、嗜酸性粒细胞、M2巨噬细胞、单核细胞、休止期CD4^(+)记忆T细胞。且qRT-PCR显示NOP2在肝癌中呈高表达,在癌旁呈低表达。结论:NOP2在肝癌中呈高表达,且与生存时间成负相关,其表达水平可有助于预测肝癌病人的预后,尤其是对于肿瘤微环境中免疫相关细胞的影响。

Objective:To explore the value of NOP2 in the prognosis of liver cancer based on bioinformatics.Methods:Two main scores of tumor infiltrating immune cells(TICs)were calculated by CIBERSORT and ESTIMATE in 497 patients with liver cancer,54 of whom had paracancerous tissue.The differentially expressed genes(DEGs)were found by Cox regression analysis.At the same time,qRT-PCR analysis was performed on 10 primary liver cancer patients undergoing hepatectomy in the First Affiliated Hospital of Bengbu Medical College.Results:The expression of NOP2 was positively correlated with the pathological features of liver cancer(late M stage)and negatively correlated with the survival time of patients.Through gene set enrichment analysis(GSEA),it was found that the genes with high NOP2 expression were mainly enriched in immune-related pathways.Further study confirmed that there was a positive correlation between the expression of NOP2 and six kinds of immune cells,which included M0 macrophages,resting natural killer cells,activated CD4^(+)memory T cells,CD8^(+)T cells,follicular helper T cells,and regulatory T cells.The expression of NOP2 was negatively correlated with the expression of five types of immune cells,including memory B cells,eosinophil granulocyte cells,M2 macrophages,monocytes,and resting CD4+memory T cells.Moreover,qRT-PCR showed that NOP2 was highly expressed in liver cancer and low expression in adjacent tissues.Conclusions:NOP2 is highly expressed in liver cancer and negatively correlated with survival time.The expression of NOP2 may be helpful to predict the prognosis of liver cancer patients,especially to the influence of immune-related cells in tumor microenvironment.