ε和δ亚型微管蛋白复合物2在肝细胞癌中的表达及其与患者预后的关系
作者:
作者单位:

西安交通大学第一附属医院 肝胆外科,陕西 西安 710000

作者简介:

肖雪莲,西安交通大学第一附属医院技师,主要从事肝癌疾病发生发展机制方面的研究。

通信作者:

涂康生,Email: tks0912@foxmail.com

基金项目:

陕西省自然科学基金资助项目(2020JC-36)。


Expression of tubulin ε and δ complex 2 in hepatocellular carcinoma and its relation with prognosis of patients
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Affiliation:

Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710000, China

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    摘要:

    背景与目的 肝癌(肝细胞癌占75%~85%)每年的新发病例数及死亡例数在我国所有癌症类型中高居第五和第二位,肝癌生长、转移、免疫逃逸及治疗抵抗的分子机制复杂,是目前研究的热点及难点。研究发现ε和δ亚型微管蛋白复合物2(TEDC2)在多种恶性肿瘤中表达上调,且与预后相关,但目前肝癌中的临床意义尚未见报道,因此,本研究探讨TEDC2在肝癌中的表达及其与患者预后的关系。方法 从TCGA和ICGC数据库中下载肝癌患者的转录组数据及临床病理资料,通过GEPIA2网站对TEDC2行泛癌分析,用Kaplan-Meier法分析TEDC2表达与患者预后的关系,用单因素和多因素Cox回归模型分析患者的预后因素,用基因富集分析探索TEDC2表达相关的生物学功能。结果 泛癌分析发现TEDC2是肾上腺皮质癌(ACC)、肾透明细胞癌(KIRC)、肾乳头状细胞癌(KIRP)、急性髓细胞样白血病(LAML)、肝癌(LIHC)和肺腺癌(LUAD)这6种癌症的风险预后因子。TCGA和ICGC数据分析均表明肝癌组织中的TEDC2表达水平高于正常组织(均P<0.05)。TEDC2的表达水平与TNM分期、T分期、组织学分级有关(均P<0.05),与性别、年龄无关(均P>0.05)。生存分析显示,TEDC2高表达的患者总生存期和无病生存期短于TEDC2低表达的患者(均P<0.05)。单因素和多因素Cox回归分析发现,TNM分期、T分期、TEDC2表达是肝癌预后的风险因素,而仅TEDC2表达在TCGA和ICGC患者中均是肝癌的独立预后因子(均P<0.05)。基因富集分析发现在TEDC2高表达样本中富集细胞增殖相关的通路。结论 TEDC2在肝癌组织中高表达,并且是肝癌的独立预后因子,其高表达与患者的不良预后密切相关,而且,机制可能与细胞增殖活性增加有关。

    Abstract:

    Background and Aims The numbers of new cases and deaths of liver cancer (hepatocellular carcinoma accounts for 75%-85%) per year rank the fifth and second among those of all cancers diagnosed in China. The molecular mechanisms for HCC growth, metastasis, immune escape and treatment resistance are complex, which are the current research hotspots and difficult issues. Studies have demonstrated that the expression of tubulin ε and δ complex 2 (TEDC2) is up-regulated in a variety of malignant tumors and is associated with the prognosis. However, the clinical significance of TEDC2 in HCC has not yet been described. Therefore, this study was conducted to explore the expression of TEDC2 in HCC and its relation with the prognosis of patients.Methods The transcriptional profiles and clinicopathologic data of liver cancer were downloaded from TCGA and ICGC databases. The pan-cancer expression analysis of TEDC2 was performed through the GEPIA2 website. The relationship between TEDC2 expression and the prognosis of patients was analyzed by Kaplan-Meier method. The prognostic factors for patients were determined by univariate and multivariate Cox analyses. The biological functions associated with the expression of TEDC2 were analyzed by gene set enrichment analysis (GSEA).Results Pan-cancer analysis showed that TEDC2 was a risk factor for 6 different cancers that included ACC (adrenocortical carcinoma), KIRC (kidney renal clear cell carcinoma), KIRP (kidney renal papillary cell carcinoma), LAML (acute myeloid leukemia), LIHC (liver hepatocellular carcinoma), LUAD (lung adenocarcinoma). Analyses of data from both TCGA and ICGC showed that TEDC2 expression in liver cancer tissues was significantly higher than that in normal tissues (both P<0.05). The expression of TEDC2 was related to TNM stage, T stage ang histological grade (all P<0.05), and was not associated with sex and age (both P>0.05). Survival analysis found that patients with high TEDC2 expression had shorter overall survival and disease-free survival than those with low TEDC2 expression (both P<0.05). Univariate and multivariate Cox analyses identified that TNM stage, T stage and TEDC2 expression were prognostic risk factors for HCC, but only TEDC2 expression was an independent prognostic factor in both TCGA and ICGC cohorts (all P<0.05). Results of GSEA showed that pathways related to cell proliferation were enriched in the tissues with high TEDC2 expression.Conclusion The expression of TEDC2 is increased in liver cancer tissue, and is an independent prognostic factor for liver cancer. Its high expression is closely associated with the unfavorable prognosis of patients, and the mechanism may be related to the enhanced activity of cell proliferation.

    图1 TEDC2在泛癌中的表达和预后情况 A:TEDC2在泛癌中的表达情况;B:TEDC2预测泛癌的OS和DFS的生存热图Fig.1 The expression and prognostic value of TEDC2 in pan-cancer samples A: The expression of TEDC2 in pan-cancer samples; B: Survival map of TEDC2 in predicting OS and DFS in pan-cancer samples
    图2 TEDC2 mRNA在肝癌组织和正常组织中的表达 A:TCGA数据;B:ICGC数据Fig.2 The expression of TEDC2 in HCC tissues and normal tissues A: TCGA database; B: ICGC database
    图3 不同TEDC2表达水平患者的生存曲线 A:基于TEDC2表达的TCGA肝癌患者的OS曲线和DFS曲线;B:基于TEDC2表达的 ICGC肝癌患者的OS曲线Fig.3 The survival curves of liver cancer patients with different levels of TEDC2 A: OS and DFS curves for the liver cancer patients in TCGA based on the expression of TEDC2; B: OS curve for liver cancer patients in ICGC based on the expression of TEDC2
    图4 肝癌患者预后的单因素和多因素Cox回归分析的森林图 A:对TCGA肝癌患者进行单因素和多因素分析;B:对ICGC肝癌患者进行单因素和多因素分析Fig.4 Forest plot of univariate and multivariate Cox regression analysis of the prognosis of liver cancer patients A: Univariate and multivariate Cox regression analysis of liver cancer patients in TCGA; B: Univariate and multivariate Cox regression analysis of liver cancer patients in ICGC
    图5 基于TEDC2表达的GSEA分析 A:基于TCGA数据的GO和KEGG分析;B:基于ICGC数据的GO和KEGG分析Fig.5 GSEA analysis based on the expression of TEDC2 A: GO and KEGG analysis based on TCGA data; B: GO and KEGG analysis based on ICGC data
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肖雪莲,涂康生.ε和δ亚型微管蛋白复合物2在肝细胞癌中的表达及其与患者预后的关系[J].中国普通外科杂志,2022,31(7):905-912.
DOI:10.7659/j. issn.1005-6947.2022.07.007

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  • 收稿日期:2021-10-11
  • 最后修改日期:2022-06-17
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  • 在线发布日期: 2022-07-31