首页|生物信息学分析前折叠蛋白家族在肝细胞癌中的表达及临床意义

生物信息学分析前折叠蛋白家族在肝细胞癌中的表达及临床意义

Bioinformatics analysis of the expression level and clinical significance of prefoldin family in hepatocellular carcinoma

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目的:采用生物信息学方法分析前折叠蛋白(PFDs)家族在肝细胞癌(肝癌)中的表达及预后价值。方法:利用GEPIA2数据库获取PFDs家族成员的mRNA在肝癌中的表达数据及其与临床分期的相关性数据。通过UALCAN数据库分析PFDs家族成员的表达与肿瘤分级之间的相关性。利用HPA数据库获取PFDs家族成员在肝癌组织和正常肝组织的免疫组化图像并进行对比分析。利用Kaplan-Meier plotter数据库分析PFDs家族成员表达对肝癌患者生存的影响,同时从TCGA下载肝癌患者相关临床数据,对PFDs家族成员和其他相关病理参数进行多因素Cox回归分析。利用DAVID 6.8生物信息学工具对PFDs家族蛋白进行富集分析。通过TIMER 2.0数据库分析PFDs家族成员的表达与肝癌免疫浸润的关系。结果:PFDN1、PFDN2、PFDN3、PFDN4的mRNA和蛋白在肝癌组织中表达水平明显高于正常肝组织(P<0.05),并与肝癌患者肿瘤分级和临床分期成正相关(P<0.05)。PFDN1、PFDN2、PFDN3、PFDN4基因过表达肝癌患者的生存时间更短(HR=1.47,1.45,1.61,1.66;P<0.05)。PFDN1、PFDN2、PFDN4为肝癌患者预后的独立影响因素(HR=1.58,1.64,2.04;P<0.05)。基因本体(GO)和KEGG通路分析表明,PFDs家族分子主要发挥着RNA和mRNA的剪切和分解功能,并参与RNA运输、mRNA监控途径和真核生物的核糖体合成等相关信号通路。PFDs家族成员的表达还与肝癌中辅助T细胞(Th)2、CD56+NK细胞和浆细胞样树突状细胞的表达成正相关,而与Th17、中性粒细胞和中央记忆T细胞的表达成负相关。结论:PFDs家族在肝癌组织中高表达,与患者不良预后有关。PFDs生物学功能与剪接体及免疫细胞浸润密不可分。
Objective:To analyze the expression level and prognostic value of prefoldins (PFDs) family in hepatocellular carcinoma (HCC) by bioinformatics approach.Methods:GEPIA2 database was employed to obtain the mRNA expression data of PFDs family members in HCC and its correlation with clinical staging. The correlation between the expression levels of PFDs family members and tumor grading was analyzed by UALCAN database. Immunohistochemical images of PFDs family members in HCC and normal liver tissues were obtained and compared by HPA database. The effect of PFDs family members expression on the survival of HCC patients was assessed by Kaplan-Meier plotter database. Clinical data of HCC patients were downloaded from TCGA. PFDs family members and related pathological parameters were subjected to multivariate Cox's regression analysis. Enrichment analysis of PFDs family proteins was carried out by DAVID 6.8 bioinformatics tool. The relationship between the expression levels of PFDs family members and immune infiltration of HCC was analyzed by TIMER 2.0 database.Results:The expression levels of PFDN1, PFDN2, PFDN3 and PFDN4 mRNA and protein in HCC tissues were significantly higher than those in normal liver tissues (P<0.05), which were positively correlated with tumor grading and clinical staging of HCC patients (P<0.05). The survival time of HCC patients with overexpression of PFDN1, PFDN2, PFDN3 and PFDN4 genes was significantly shorter (HR=1.47, 1.45, 1.61, 1.66; P<0.05). PFDN1, PFDN2 and PFDN4 were the independent prognostic factors of HCC patients (HR=1.58, 1.64, 2.04; P<0.05). Gene ontology (GO) and KEGG pathway analyses showed that PFDs family molecules played a role in RNA and mRNA splicing and decomposition, and participated in RNA transport, mRNA monitoring pathway and ribosome synthesis in eukaryotes and other related signaling pathways. The expression of PFDs family members was positively correlated with the expression of helper T cells (Th) 2, CD56+NK cells and plasma cell-like dendritic cells in HCC, whereas negatively associated with the expression of Th17, neutrophils and central memory T cells.Conclusions:High expression of PFDs family members in HCC tissues is correlated with the poor prognosis of HCC patients. The biological function of PFDs is intimately associated with splicer and immune cell infiltration.

李福平、王茂、程瑞、李尚朋、代引海

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712046 陕西省咸阳市,陕西中医药大学第二临床医学院

712000 陕西省咸阳市,陕西中医药大学第二附属医院肿瘤乳腺外科

癌,肝细胞 前折叠蛋白 预后 计算生物学

陕西省科技厅重点研发计划项目陕西中医药大学学科创新团队项目

2022SF-5632019-SY03

2023

中华肝脏外科手术学电子杂志
中华医学会

中华肝脏外科手术学电子杂志

CSTPCD
影响因子:0.822
ISSN:2095-3232
年,卷(期):2023.12(2)
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