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中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2024, Vol. 13 ›› Issue (03) : 363 -369. doi: 10.3877/cma.j.issn.2095-3232.2024.03.018

基础研究

CDC42EP2基因与肝癌预后、免疫细胞浸润关系及其对细胞迁移侵袭的影响
曾谣1, 谢琴2, 陈显育3, 王平根2, 毛玲秋2, 何丹玲2, 杜飞2, 郑希彦2, 何函樨2,†()   
  1. 1. 518000　深圳，中山大学附属第八医院运动医学科
    2. 518000　深圳，中山大学附属第八医院肝胆胰外科
    3. 510630　广州，中山大学附属第三医院肝胆外科
  • 收稿日期:2024-02-25 出版日期:2024-06-10
  • 通信作者: 何函樨
  • 基金资助:
    深圳市科技创新委基础研究面上项目(JCYJ20220530144404011)

Relationship between CDC42EP2 gene and prognosis of hepatocellular carcinoma, immune cell infiltration and its effects on cell migration and invasion

Yao Zeng1, Qin Xie2, Xianyu Chen3, Pinggen Wang2, Lingqiu Mao2, Danling He2, Fei Du2, Xiyan Zheng2, Hanxi He2,†()   

  1. 1. Department of Sports Medicine, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518000, China
    2. Department of Hepatobiliary and Pancreatic Surgery, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518000, China
    3. Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2024-02-25 Published:2024-06-10
  • Corresponding author: Hanxi He
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引用本文：

曾谣, 谢琴, 陈显育, 王平根, 毛玲秋, 何丹玲, 杜飞, 郑希彦, 何函樨. CDC42EP2基因与肝癌预后、免疫细胞浸润关系及其对细胞迁移侵袭的影响[J]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 363-369.

Yao Zeng, Qin Xie, Xianyu Chen, Pinggen Wang, Lingqiu Mao, Danling He, Fei Du, Xiyan Zheng, Hanxi He. Relationship between CDC42EP2 gene and prognosis of hepatocellular carcinoma, immune cell infiltration and its effects on cell migration and invasion[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(03): 363-369.

目的

探讨CDC42EP2基因与肝细胞癌（肝癌）患者预后和免疫细胞浸润的关系及其对细胞迁移侵袭的影响。

方法

从癌症基因组图谱（TCGA）数据库下载肝癌组织与正常肝组织中CDC42EP2基因表达谱数据，分析肝癌组织CDC42EP2基因表达与临床病理特征的相关性，并用Kaplan-Meier Plotter数据库进行生存预后分析；利用HCCDB数据库分析CDC42EP2的共表达网络；利用TIMER2.0数据库探讨CDC42EP2表达与免疫细胞浸润的相关性；采用siRNA技术抑制HepG2肝癌细胞中CDC42EP2基因表达，qRT-PCR及Transwell实验分别检测CDC42EP2对肝癌细胞迁移和侵袭能力的影响。

结果

TCGA数据库分析显示，肝癌组织CDC42EP2表达明显高于正常肝组织（P<0.05），肝癌组织CDC42EP2表达与肝癌病理组织学分级、TNM分期、TP53突变相关（P<0.05）。肝癌组织CDC42EP2高表达患者中位生存时间为41.0个月，明显低于低表达患者的84.4个月（HR=1.86，P<0.05）。CDC42EP2表达与辅助性T细胞（Th）、中央记忆型T细胞（Tcm）及Th2细胞浸润成正比，而与树突状细胞（DC）及Th17细胞浸润成反比（r=0.179，0.172，0.144，-0.125，-0.182；P<0.05）。siRNA敲低CDC42EP2基因后，HepG2肝癌细胞迁移和侵袭能力显著降低。

结论

肝癌组织CDC42EP2基因高表达，其高表达与肝癌预后不良有关。敲低CDC42EP2基因可抑制肝癌细胞的迁移和侵袭能力。

关键词: 癌，肝细胞, 细胞分裂周期蛋白42（CDC42）, CDC42效应蛋白2, 预后, 免疫浸润, 侵袭
Objective

To investigate the relationship between CDC42EP2 gene and prognosis, immune cell infiltration in patients with hepatocellular carcinoma (HCC) and its effects on cell migration and invasion.

Methods

The expression profile data of CDC42EP2 gene in HCC and normal liver tissues were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between CDC42EP2 gene expression in HCC tissues and clinicopathological characteristics was analyzed. Survival analysis was performed by Kaplan-Meier Plotter. The co-expression network of CDC42EP2 was determined by using HCCDB database. The correlation between CDC42EP2 expression and immune cell infiltration was evaluated by using TIMER2.0 database. The expression of CDC42EP2 gene in HepG2 cells was suppressed by siRNA technology. The effects of CDC42EP2 on cell migration and invasion were assessed byqRT-PCR and Transwell chamber assay.

Results

TCGA database analysis showed that the expression level of CDC42EP2 in HCC tissues was significantly higher than that in normal liver tissues (P<0.05). Expression of CDC42EP2 in HCC tissues was correlated with histopathological grade, TNM stage and TP53 mutation (P<0.05). The median survival of patients with high expression of CDC42EP2 in HCC tissues was 41.0 months, significantly shorter than 84.4 months of those with low CDC42EP2 expression (HR=1.86, P<0.05). The expression level of CDC42EP2 was positively associated with the infiltration of helperT cells (Th), central memory T cells (Tcm) and Th2 cells, but negatively associated with the infiltration of dendritic cells (DC) and Th17 cells (r=0.179, 0.172, 0.144, -0.125, -0.182; P<0.05). After CDC42EP2 gene was knockdowned by siRNA technology, the migration and invasion capabilities of HepG2 cells were significantly weakened.

Conclusions

CDC42EP2 gene is highly expressed in HCC, which is correlated with poor prognosis of HCC patients. Knockdown of CDC42EP2 gene can inhibit the migration and invasion of HCC cells.

Key words: Carcinoma, hepatocellular, Cell division cycle 42 (CDC42), CDC42 effector protein 42, Prognosis, Immune infiltration, Invasion
图1 TCGA数据库肝癌组织中CDC42EP2的表达注：a为TCGA数据库示肝癌组织中CDC42EP2 mRNA高表达；b为免疫组化法检测示肝癌组织CDC42EP2蛋白高表达；CDC42EP2为细胞分裂周期42效应因子蛋白2，TCGA为癌症基因组图谱，***为P<0.001
图2 TCGA数据库中CDC42EP2表达与肝癌患者临床病理特征的关系注：a、b、c分别示CDC42EP2 mRNA表达与肝癌病理组织学分级、TNM分期和TP53突变相关；CDC42EP2为细胞分裂周期42效应因子蛋白2，*为P<0.05，**为P<0.01
图3 TCGA数据库中CDC42EP2 mRNA表达水平与肝癌患者预后的关系注：CDC42EP2高表达与肝癌患者预后不良相关；CDC42EP2为细胞分裂周期42效应因子蛋白2，TCGA为癌症基因组图谱
图4 CDC42EP2在肝癌组织的共表达分析及免疫细胞浸润的相关性注：a为HCCDB数据库分析CDC42EP2的共表达网络，b为棒棒图示肝癌组织中CDC42EP2表达与肿瘤免疫细胞浸润的相关性；CDC42EP2为细胞分裂周期42效应因子蛋白2，Th为辅助性T细胞，Tcm为中央记忆型T细胞，Tem为效应记忆T细胞，Tgd为γδT细胞，TFH为滤泡辅助T细胞，TReg为调节性T细胞，DC为树突状细胞，aDC、iDC、pDC分别为活化的树突状细胞、间质性树突状细胞、浆细胞样树突状细胞
图5 敲低CDC42EP2显著抑制肝癌HepG2细胞迁移及侵袭能力注：a为qRT-PCR检测LO2、Hep3B、HepG2及Huh7细胞系中CDC42EP2 mRNA表达量；b为qRT-PCR检测HepG2细胞系转染siCDC42EP2后CDC42EP2 mRNA表达量变化；c为Transwell实验检测HepG2细胞转染siCDC42EP2后迁移及侵袭的变化；**为P<0.01，ns为差异无统计学意义
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