基于生物信息学方法分析E3泛素连接酶DTL在肝细胞癌中的表达与预后意义

肝癌电子杂志 ›› 2022, Vol. 9 ›› Issue (1): 41-47.

基于生物信息学方法分析E3泛素连接酶DTL在肝细胞癌中的表达与预后意义

刘振荣, 肖汀^*

国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院分子肿瘤学国家重点实验室/癌发生及预防分子机理北京市重点实验室,北京 100021

收稿日期:2021-12-24 出版日期:2022-03-31 发布日期:2022-10-28
通讯作者: ^*肖汀,E-mail：xiaot@cicams.ac.cn
作者简介:刘振荣, 硕士研究生, 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 分子肿瘤学国家重点实验室
基金资助:
中国医学科学院医学与健康科技创新工程（2021-1-I2M-050）

Analysis of the expression and prognostic significance of dentideless E3 ubiquitin ligase in hepatocellular carcinoma based on bioinformatics methods

Liu Zhenrong, Xiao Ting^*

State Key Laboratory of Molecular Oncology, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100021, China

Received:2021-12-24 Online:2022-03-31 Published:2022-10-28

摘要/Abstract

摘要： 目的: 探讨E3泛素连接酶DTL（dentideless E3 ubiquitin ligase）在肝细胞癌（hepatocellular carcinoma,HCC）组织中的表达及预后价值。
方法: 从癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库中下载获得374例HCC组织和50例癌旁正常组织的转录组数据;从基因表达综合数据库（Gene Expression Omnibus,GEO）下载GSE121248数据集,获得包括70例HCC组织和37例癌旁正常组织的转录组数据。比较HCC组织与癌旁正常组织中DTL的表达水平。采用Kaplan-Meier法进行生存分析,并采用log-rank检验比较DTL高表达组与DTL低表达组HCC患者总生存率、无进展间期生存率的差异。HCC患者不良预后的危险因素采用Cox回归分析。绘制DTL表达水平诊断HCC的受试者操作特征（receiver operator characteristic,ROC）曲线。利用基于多因素Cox回归分析的列线图预测DTL对HCC患者预后的影响。同时对DTL高表达组与DTL低表达组HCC组织的差异表达基因进行GSEA富集分析。
结果: DTL在HCC组织中的表达水平高于癌旁正常组织（P<0.001）。DTL高表达组与DTL低表达组HCC患者年龄、人种、AFP水平、病理分级、病理分期、T分期差异均有统计学意义（P均<0.05）。Kaplan-Meier法生存分析结果显示,与DTL低表达组HCC患者相比,DTL高表达组HCC患者总生存率和无进展间期生存率均较短（P=0.005,P<0.001）。ROC曲线显示,DTL表达水平对HCC有较强的诊断能力[曲线下面积（area under the curve,AUC）为0.96]。通过构建列线图发现,DTL表达的C指数为0.663（95%CI为0.54~0.61）。GSEA富集分析结果显示,DTL可能通过影响细胞周期、染色体维持、DNA复制、G2/M检查点、有丝分裂期、TP53转录调控等通路影响HCC的发生发展。

关键词: DTL, 肝细胞癌, 预后

Abstract: Objective:To investigate the expression and prognostic value of dentideless E3 ubiquitin ligase (DTL) in hepatocellular carcinoma (HCC).
Method:Transcriptome data of 374 HCC tissues and 50 paracancer tissues were downloaded from The Cancer Genome Atlas (TCGA) database. The GSE121248 dataset was downloaded from the Gene Expression Omnibus (GEO) database, and transcriptome data including 70 HCC tissues and 37 paracancer normal tissues was obtained. The expression level of DTL in HCC tissues was compared with that in normal adjacent tissues. Kaplan-meier method was used for survival analysis, and log-rank test was used to compare the overall survival rate and progression-free interval rate of HCC patients between the DTL high expression group and the DTL low expression group. The risk factors for poor prognosis of HCC patients were analyzed by Cox regression analysis. The receiver operator characteristic (ROC) curve of DTL expression level for HCC diagnosis was plotted. The effect of DTL on the prognosis of HCC patients was predicted by using multivariate Cox regression analysis. Meanwhile, GSEA enrichment analysis was performed for differentially expressed genes in HCC tissues of DTL high expression group and DTL low expression group.
Result:The expression level of DTL in HCC tissues was higher than that in adjacent normal tissues (P<0.001). There were statistically significant differences in age, race, AFP level, histologic grade, pathological stage and T stage between the DTL high expression group and the DTL low expression group (P<0.05). Kaplan-meier survival analysis showed that overall survival and progression-free survival were shorter in HCC patients with high DTL expression compared with HCC patients with low DTL expression (P=0.005, P<0.001). ROC curve showed that DTL expression level had strong diagnostic ability for HCC [area under the curve (AUC) was 0.96]. The c-index of DTL expression was 0.663 (95%CI 0.54~0.61). GSEA enrichment analysis showed that DTL may affect the occurrence and development of HCC through the influence of cell cycle, chromosome maintenance, DNA replication, G2/M checkpoint, mitotic stage, TP53 transcription regulation and other pathways.
Conclusion:High expression of DTL predicts poor prognosis of hepatocellular carcinoma, suggesting that DTL may be a potential biomarker for diagnosis and prognosis of hepatocellular carcinoma.

Key words: Dentideless E3 ubiquitin ligase, Hepatocellular carcinoma, Prognosis

刘振荣, 肖汀. 基于生物信息学方法分析E3泛素连接酶DTL在肝细胞癌中的表达与预后意义[J]. 肝癌电子杂志, 2022, 9(1): 41-47.

Liu Zhenrong, Xiao Ting. Analysis of the expression and prognostic significance of dentideless E3 ubiquitin ligase in hepatocellular carcinoma based on bioinformatics methods[J]. Electronic Journal of Liver Tumor, 2022, 9(1): 41-47.

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