Chinese Medical Sciences Journal ›› 2022, Vol. 37 ›› Issue (4): 331-339.doi: 10.24920/004006

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TOP2A基因对预测肝细胞癌预后的作用

陆进1,2,安韶光3,马俊杰3,杨月4,张磊5,俞鹏1,陶恒1,陈云帆1,张浩轩1,2,*()   

  1. 1蚌埠医学院 基础医学院, 安徽, 蚌埠 233030
    2蚌埠医学院 数字医学与智慧健康安徽省重点实验室, 安徽, 蚌埠 233030
    3蚌埠医学院 临床医学院, 安徽, 蚌埠 233030
    4蚌埠医学院 第一附属医院耳鼻喉科, 安徽, 蚌埠 233030
    5蚌埠医学院 第二附属医院肿瘤外科, 安徽, 蚌埠 233030
  • 收稿日期:2021-09-22 接受日期:2021-12-10 出版日期:2022-12-31 发布日期:2022-10-04
  • 通讯作者: 张浩轩 E-mail:0100197@bbmc.edu.cn

Topoisomerase α Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis

Jin Lu1,2,Shaoguang An3,Junjie Ma3,Yue Yang4,Lei Zhang5,Peng Yu1,Heng Tao1,Yunfan Chen1,Haoxuan Zhang1,2,*()   

  1. 1School of Basic Medicine, Bengbu Medical College, Bengbu, Anhui 233030, China
    2Anhui Key Laboratory of Computational Medicine and Intelligent Health, Bengbu Medical College, Bengbu, Anhui 233030, China
    3Clinical Medical College, Bengbu Medical College, Bengbu, Anhui 233030, China
    4Department of Otolaryngology, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui 233030, China
    5Department of Surgical Oncology, Second Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui 233030, China
  • Received:2021-09-22 Accepted:2021-12-10 Published:2022-12-31 Online:2022-10-04
  • Contact: Haoxuan Zhang E-mail:0100197@bbmc.edu.cn

摘要:

目的 研究拓扑异构酶Ⅱα(topoisomerase II αTOP2α)基因在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及其在预测HCC患者预后中的作用。
方法 我们利用UALCAN、HCCDB、cBioPortal和Enrichr数据库中的HCC相关数据集,分析TOP2α及其共表达基因在HCC组织中的表达和突变情况,以及TOP2α及其共表达基因的GO功能和KEGG通路富集情况。利用TIMER数据库分析HCC组织中浸润的免疫细胞水平。采过Kaplan-Meier分析TOP2α及其共同表达基因与浸润的免疫细胞对HCC患者生存的影响。
结果 TOP2α及其共同表达基因在HCC组织中高表达(P < 0.001),并与HCC患者的总生存期缩短有关(P < 0.0001)。TOP2α及其共表达基因主要参与细胞有丝分裂和增殖以及细胞周期通路过程(ID:hsa04110,P = 0.001945)。TOP2α及其共同表达基因的突变与HCC患者的总生存期(P = 0.0247)和无病生存期(P = 0.0265)的缩短有关。TOP2α与HCC肿瘤组织中B细胞(r = 0.459, P < 0.01)、CD8+ T细胞(r = 0.312, P < 0.01)、CD4+ T细胞(r = 0.370, P < 0.01)、巨噬细胞(r = 0.459, P < 0.01)、中性粒细胞(r = 0.405, P < 0.01)和树突状细胞(r = 0.473, P < 0.01)的浸润量呈正相关。CD8+ T细胞的浸润能显著延长HCC患者3年和5年生存期(P均 < 0.05),而CD4+ T细胞的浸润能显著缩短HCC患者的3、5和10年生存期(P均 < 0.05)。
结论 TOP2α可能是一种癌基因,与HCC患者预后不良有关,其可能成为预测肝细胞癌患者预后的生物标志物。

关键词: 拓扑异构酶Ⅱ α, 无病生存, 总体生存, 肝细胞癌, 生物信息学分析

Abstract:

Objective To investigate the expression of topoisomeraseα (TOP2α) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients.
Methods We used HCC-related datasets in UALCAN, HCCDB, and cBioPortal databases to analyze the expression and mutation of TOP2α and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of TOP2α and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of TOP2α and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by Kaplan-Meier plotter analysis.
Results TOP2α and its co-expression genes were highly expressed in HCC (P< 0.001) and detrimental to overall survival of HCC patients (P< 0.001). TOP2α and its co-expression genes were mainly involved in cell mitosis and proliferation, and cell cycle pathway (ID: hsa04110, P = 0.001945). TOP2α and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (P = 0.0247) and disease-free survival (P = 0.0265) of HCC patients. High TOP2α expression was positively correlated with the infiltration of B cell (r = 0.459, P< 0.01), CD8+ T cell (r = 0.312, P< 0.01), CD4+ T cell (r = 0.370, P< 0.01), macrophage (r = 0.459, P< 0.01), neutrophil (r = 0.405, P< 0.01), and dendritic cell (r = 0.473, P< 0.01) in HCC. The CD8+ T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all P< 0.05), and CD4+ T cell infiltration significantly shortened the 3-, 5-, and 10-year survival of HCC patients (all P< 0.05).
Conclusion TOP2α may be an oncogene, which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.

Key words: topoisomeraseⅡα, disease-free survival, overall survival, hepatocellular carcinoma, bioinformatics analysis

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