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中华肝脏外科手术学电子杂志 ›› 2021, Vol. 10 ›› Issue (06) : 636 -641. doi: 10.3877/cma.j.issn.2095-3232.2021.06.021

基础研究

生物信息学分析DHX9在肝细胞癌中表达及临床意义
袁晓峰1, 徐雯1, 闫凌1, 毕筱刚1, 李明亮1,()   
  1. 1. 510530 广州,中山大学附属第三医院岭南医院综合ICU
  • 收稿日期:2021-08-16 出版日期:2021-09-23
  • 通信作者: 李明亮

Bioinformatics analysis of DHX9 expression in hepatocellular carcinoma and clinical significance

Xiaofeng Yuan1, Wen Xu1, Ling Yan1, Xiaogang Bi1, Mingliang Li1,()   

  1. 1. General ICU, Lingnan Hospital of the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510530, China
  • Received:2021-08-16 Published:2021-09-23
  • Corresponding author: Mingliang Li
引用本文:

袁晓峰, 徐雯, 闫凌, 毕筱刚, 李明亮. 生物信息学分析DHX9在肝细胞癌中表达及临床意义[J/OL]. 中华肝脏外科手术学电子杂志, 2021, 10(06): 636-641.

Xiaofeng Yuan, Wen Xu, Ling Yan, Xiaogang Bi, Mingliang Li. Bioinformatics analysis of DHX9 expression in hepatocellular carcinoma and clinical significance[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2021, 10(06): 636-641.

目的

探讨DEAH盒解旋酶9 (DHX9)在肝细胞癌(肝癌)早期诊断和治疗中的作用。

方法

利用GEPIA、Oncomine、The Human Protein Atlas在线平台从DNA、mRNA和蛋白质3个层面分析肝癌组织和正常肝组织中DHX9的表达情况。通过UALCAN、Kaplan-Meier Plotter在线平台分析DHX9与肝癌临床特征和预后的关系。cBioPortal在线平台分析肝癌中的DHX9基因突变情况,LinkedOmics、WebGestalt在线平台分析DHX9基因的生物学意义。STRING在线平台构建DHX9蛋白相互作用网络。

结果

GEPIA、Oncomine、The Human Protein Atlas在线平台分析结果显示,与正常肝组织相比,DHX9 mRNA、DHX9 DNA、DHX9蛋白质在肝癌中明显高表达。DHX9 mRNA表达与年龄、TP53突变、疾病分期和肿瘤分级有关。Kaplan-Meier Plotter在线平台分析显示,DHX9 mRNA低表达肝癌患者的总体生存、疾病特异性生存和无进展生存预后更好(HR=1.48,1.62,1.57;P<0.05)。DHX9基因突变发生率17%(63/370),大多数基因突变为扩增和mRNA增高。DHX9基因突变的表达水平与肿瘤组织学分级有关(P=0.017)。DHX9基因主要参与DNA修复、有丝分裂、DNA代谢、细胞周期调控、解螺旋酶活性、转录因子结合等活动。京都基因与基因组百科全书(KEGG)通路分析显示,DHX9基因在mRNA监测通路、RNA转运、酪氨酸代谢、过氧化物酶体增殖物激活受体(PPAR)信号通路等中富集。DHX9蛋白参与DNA修复途径,促进核糖体招募、翻译起始,细胞的生长和分裂等活动。

结论

DHX9基因主要参与DNA修复、RNA转运、细胞周期调控、PPAR信号通路等重要生物学过程。DHX9在肝癌组织中高表达,与肿瘤分级、分期有关,且低表达患者生存预后较好。

Objective

To investigate the role of DEAH-box helicase 9 (DHX9) in the early diagnosis and treatment of hepatocellular carcinoma (HCC).

Methods

The expression profile of DHX9 in the HCC and normal liver tissues was analyzed from the DNA, mRNA and protein aspects on GEPIA, Oncomine and The Human Protein Atlas. The relationship between DHX9 and clinical features and prognosis of HCC patients was analyzed with UALCAN and Kaplan-Meier Plotter online analysis tools. DHX9 gene mutation in HCC was analyzed on cBioPortal. The biological significance of DHX9 gene was analyzed on LinkedOmics and WebGestalt. The DHX9 protein interaction network was constructed by STRING online analysis tool.

Results

The expression levels of DHX9 mRNA, DHX9 DNA and DHX9 protein in the HCC tissues were significantly higher compared with those in the normal liver tissues according to the analysis results of GEPIA, Oncomine and The Human Protein Atlas. The expression level of DHX9 mRNA was associated with age, TP53 mutation, disease staging and tumor grading. The overall survival, disease-specific survival and progression-free survival of HCC patients with low expression of DHX9 mRNA were better based on the analysis of Kaplan-Meier Plotter (HR=1.48, 1.62, 1.57; P<0.05). The mutation rate of DHX9 gene was 17%(63/370), and a majority of the mutations were amplification and mRNA increase. The expression level of DHX9 gene mutation was correlated with the histological grading of tumors (P=0.017). DHX9 gene was mainly involved in DNA repair, mitosis, DNA metabolism, cell cycle regulation, helicases activity and transcriptional factor-binding capability, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis revealed that DHX9 gene was enriched in the mRNA monitoring pathway, RNA transport, tyrosine metabolism and peroxisome proliferators-activated receptor (PPAR) signaling pathway, etc. DHX9 protein participated in DNA repair pathway and promoted ribosome recruitment, initiation of translation, cell growth and division, etc.

Conclusions

DHX9 gene is mainly involved in DNA repair, RNA transport, cell cycle regulation, PPAR signaling pathway and other critical biological processes. DHX9 is highly expressed in the HCC tissues, which is associated with tumor grading and disease staging. Patients with low expression of DHX9 obtain better survival and prognosis.

图1 DHX9基因在肝癌中的表达情况注:a为DHX9 mRNA在肝癌中高表达;b为在多个肝癌组织数据库中DHX9 DNA高表达;c为患者免疫组化法检测显示DHX9蛋白质肝癌中高表达;DHX9为DEAH盒解旋酶9,TPM为transcript per million
图2 DHX9 mRNA表达水平与肝癌临床特征和预后的关系注:a、b、c、d为UALCAN网站分析显示DHX9 mRNA表达水平与肝癌患者年龄、TP53突变、肿瘤分期和分级有关;e为GEPIA网站分析显示DHX9 mRNA表达与肿瘤分期有关;f为DHX9 mRNA肝癌患者总体生存分析;*P<0.05,***P<0.001;TPM为transcript per million
图3 肝癌中DHX9基因突变情况注:a示DHX9基因突变主要是扩增和mRNA增高;b示DHX9基因突变频率与CACNA1E、HMCN1、SPTA1、TDRD5、FLG、GLUL、QSOX1、RGL1、RGSL1、RASAL2相关;c示DHX9基因突变水平与肿瘤组织学分级有关
图4 DHX9基因共表达基因火山图
图5 DHX9蛋白相互作用网络
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