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  • 王庆亮,赵艳峰,蒋燕,等.基于生物信息学分析的TPX2在肺腺癌中的表达及意义[J].同济大学学报(医学版),2021,42(1):11-18.    [点击复制]
  • WANG Qing-liang,ZHAO Yan-feng,JIANG Yan,et al.Expression of TPX2 in lung adenocarcinoma and its clinical significance analyzed with bioinformatics[J].同济大学学报(医学版),2021,42(1):11-18.   [点击复制]
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基于生物信息学分析的TPX2在肺腺癌中的表达及意义
王庆亮,赵艳峰,蒋燕,宋晓,杨富钧,姜格宁
0
(同济大学附属上海市肺科医院胸外科,上海200433)
摘要:
目的利用多种肿瘤生物信息数据库分析TPX2在肺腺癌样本中的表达及临床意义,并在临床病理标本中进行验证。方法通过检索Oncomine生物信息基因数据库,分析TPX2在不同肺腺癌数据集中mRNA表达情况;利用cBioportal生物信息基因数据库分析TPX2的突变频率、突变位点,并分析TPX2基因突变与预后的关系;利用HPA数据库的组织图谱分析TPX2蛋白质在肺腺癌组织中的表达情况。通过UALCAN和OncoLnc数据库检索肺腺癌与正常组织中TPX2的表达情况,分析其与肺腺癌临床病理分期的关系,并采用Kaplan-Meier在线分析TPX2表达与患者生存期的关系。通过Western印迹法实验对比肺癌患者癌组织与癌旁组织TPX2蛋白表达差异以及TPX2在不同肺癌细胞系中的表达情况。结果Oncomine数据库的结果显示,TPX2在人肺腺癌不同数据集中的表达均显著高于正常肺组织(均P<0.001),HPA数据库检索IHC实验结果显示: 与正常肺组织相比,TPX2蛋白在癌组织中的表达水平显著上调(P<0.05)。生存分析发现高表达TPX2的肺腺癌患者的生存期显著低于TPX2低表达的肺腺癌患者,TPX2高表达患者预后更差(P<0.05);cBioportal数据库分析结果显示,TPX2共有30个位点发生变异,总变异率为4%,其中有17个位点发生突变,突变频率分别为4.06%(TCGA PanCan),3.83%(Broad),且存在TPX2突变的肺腺癌患者的DFS更差(P<0.05)。在探讨TPX2在不同肺癌细胞系及肺腺癌组织和癌旁组织中的表达差异时,发现TPX2在肺鳞癌、肺腺癌、肺大细胞癌细胞系中均存在高表达,且TPX2在肺腺癌组织中的表达量显著高于癌旁组织(均P<0.05)。结论基于肿瘤生物信息库综合分析发现,TPX2在肺腺癌组织中的表达水平明显高于正常肺组织,且TPX2的其表达水平与肿瘤预后具有相关性,TPX2在肺腺癌中的高表达预示患者预后不良。
关键词:  TPX2  肺腺癌  生物信息学  预后
DOI:10.12289/j.issn.1008-0392.20236
投稿时间:2020-05-26
基金项目:
Expression of TPX2 in lung adenocarcinoma and its clinical significance analyzed with bioinformatics
WANG Qing-liang,ZHAO Yan-feng,JIANG Yan,SONG Xiao,YANG Fu-jun,JIANG Ge-ning
(Dept. of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China)
Abstract:
ObjectiveTo analyze the expression of TPX2 in lung adenocarcinoma and its clinical significance with bioinformatics. MethodsThe mRNA expression of TPX2 in different lung adenocarcinoma data sets was analyzed by searching Oncomine bioinformatics gene database; the mutation frequency and mutation site of TPX2 and its correlation with patients’ prognosis were analyzed using cBioportal bioinformatics gene database; the protein expression of TPX2 in lung adenocarcinoma tissue was analyzed using HPA tissue protein expression profiles database; the expression of TPX2 in lung adenocarcinoma and normal tissues was retrieved from UALCAN and Oncolnc databases, and the relationship between TPX2 expression and different clinicopathological stage of lung adenocarcinoma was analyzed; the relationship between TPX2 expression and patient survival time was analyzed by the Kaplan-Meier Plotter method; the protein expression of TPX2 in the tumor tissues and non-tumor adjacent tissues was examined by Western blotting; the protein expression of TPX2 in different lung cancer cell lines was measured using Western blotting. ResultsThe Oncomine dataset analysis showed that the expression of TPX2 in different data sets of human lung adenocarcinoma was significantly higher than that in normal lung tissues (all P<0.001). The IHC data retrieved from HPA dataset demonstrated that the protein expression level of TPX2 in lung adenocarcinoma tissues was significantly higher than that in normal lung tissues. Survival analysis showed that the survival time of lung adenocarcinoma patients with high TPX2 expression was significantly lower than that of patients with low TPX2 expression, and the prognosis of patients with high TPX2 expression was worse (P<0.05). The cBioportal dataset analysis showed that there were 30 sequence variation sites in TPX2 gene, with a total variation rate of 4%, in which 17 sites were mutated, with mutation frequency of 4.06%(TCGA PanCan) and 3.83%(Broad), respectively. Furthermore, patients with lung adenocarcinoma with TPX2 mutation had worse DFS (P<0.05). The validation data demonstrated that TPX2 was highly expressed in lung squamous cell carcinoma, lung adenocarcinoma and lung large cell carcinoma cell lines, and the expression level of TPX2 in lung adenocarcinoma tissues was significantly higher than that in non-tumor adjacent tissues. ConclusionThe expression level of TPX2 in lung adenocarcinoma tissue is significantly higher than that in normal lung tissue, and the expression level of TPX2 is correlated with prognosis of patients. The high TPX2 expression in lung adenocarcinoma indicates poor prognosis in patients with lung adenocarcinoma.
Key words:  TPX2  lung adenocarcinoma  bioinformatics  prognosis

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