ESPL1基因在肝细胞癌组织中的表达及其在预后评估中的作用

肝脏 ›› 2023, Vol. 28 ›› Issue (3): 285-289.

ESPL1基因在肝细胞癌组织中的表达及其在预后评估中的作用

胡伯斌, 王荣明, 梁蘅恺, 韦璐, 黎清梅, 苏土梅, 殷倩冰, 江建宁

530021 南宁广西医科大学第一附属医院感染性疾病科教育部区域性高发肿瘤早期防治研究重点实验室

收稿日期:2022-11-24 出版日期:2023-03-31 发布日期:2023-08-28
通讯作者: 江建宁,Email:jjianning@163.com
基金资助:
广西医科大学青年科学基金项目(GXMUYSF201910);国家自然科学基金(81960115);教育部区域性高发肿瘤早期防治研究重点实验室自主课题(GKE2019-04);广西病毒性肝炎防治研究重点实验室开放课题基金项目(GXCDCKL202001)

Expression of ESPL1 gene in hepatocellular carcinoma tissue and its role in the prognosis assessment

HU Bo-bin, WANG Rong-ming, LIANG Heng-kai, WEI Lu, LI Qing-mei, SU Tu-mei, YIN Qian-bing, JIANG Jian-ning

Department of Infectious Diseases, the First Affiliated Hospital of Guangxi Medical University; Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Ministry of Education, Nanning 530021, China

Received:2022-11-24 Online:2023-03-31 Published:2023-08-28
Contact: JIANG Jian-ning, Email:jjianning@163.com

摘要/Abstract

摘要： 目的探讨外纺锤体极样蛋白1(ESPL1)基因在肝细胞癌(HCC)中的表达及其对临床预后的影响,初步分析ESPL1变异情况及分子生物学功能。方法从TCGA数据库获得HCC患者ESPL1表达数据和临床信息,比较癌、癌旁及正常组织中ESPL1的表达情况。采用Cox回归分析影响HCC患者预后的危险因素,Kaplan-Meier法分析ESPL1表达水平与HCC患者预后的关系。log rank检验ESPL1高表达组和低表达组的生存差异。cBioportal在线软件分析ESPL1突变情况,通过STRING数据库绘制ESPL1蛋白互作网络,并据此进行GO|KEGG富集分析其分子生物学功能。结果肝癌组织中ESPL1表达水平高于癌旁及正常组织,分别为0.894±0.643比0.337±0.340、1.908±1.079比0.912±0.770(P＜0.05);乙型肝炎相关肝癌ESPL1水平高于非乙型肝炎相关肝癌,为2.159±1.17 比1.747±0.983(P＜0.05)。ESPL1表达水平与性别、年龄、BMI、原发肿瘤分期、AFP水平有关(P＜0.05)。原发肿瘤分期、ESPL1表达水平是HCC患者预后的独立危险因素,ESPL1表达越高,预后越差(HR=1.72,95%CI:1.21~2.41,P＜0.05)。ESPL1在HCC患者中突变率为1%,突变者预后较差。富集结果显示ESPL1主要参与细胞周期、有丝分裂、染色体分离等生物学功能。结论 ESPL1在HCC中表达上调,尤其在乙型肝炎相关肝癌中高表达具有特异性。HCC患者ESPL1高表达及存在ESPL1突变者预后较差。ESPL1可作为HCC患者不良预后的潜在标志物。

关键词: ESPL1, 肝细胞癌, 乙型肝炎, 预后

Abstract: Objective To investigate the expression of Extra spindle poles-like 1 protein (ESPL1) gene in hepatocellular carcinoma (HCC) tissues and its influence on clinical prognosis of HCC, and preliminarily analyze the variation and molecular biological function of ESPL1. Methods ESPL1 expression data and clinical information of HCC patients were obtained from the TCGA database. The expression levels of ESPL1 in cancer, paracancerous, and normal tissues were compared. The COX regression was used to investigate the risk factors of the prognosis in HCC patients, and the Kaplan-Meier method was used to investigate the relationship between the high and low ESPL1 expression level and the prognosis of HCC patients. According to the median ESPL1 expression level, the data were divided into high-expression group and low-expression group, and the log rank test was used to analyze the survival differences between the 2 groups. cBioPortal online software was used to analyze the mutation of ESPL1. The ESPL1 protein interaction network was plotted through the STRING database, and its molecular biological functions were analyzed by GO|KEGG enrichment. Results The ESPL1 expression level of liver cancer tissues was higher than that of paracancerous and normal tissues (0.894 ± 0.643 vs 0.337 ± 0.34, 1.908 ± 1.079 vs 0.912±0.77, P＜0.05), and the level of ESPL1 in hepatitis B-related liver cancer was higher than that of non-hepatitis B-related liver cancer (2.159 ± 1.17 vs 1.747 ± 0.983, P＜0.05). ESPL1 expression level was related to gender, age, body mass index (BMI), primary tumor stage, and alpha fetal protein (AFP) level (P＜0.05). Primary tumor stage and ESPL1 expression level were independent risk factors for the prognosis of HCC patients. The expression of ESPL1 was negatively correlated to the prognosis (HR=1.72, 95%CI: 1.21-2.41, P＜0.05). The mutation rate of ESPL1 in HCC patients was about 1%, and the prognosis of mutants was poor (P＜0.05). The enrichment results show that ESPL1 was mainly involved in cell cycle, mitosis, chromosome segregation and other biological functions. Conclusion ESPL1 expression level is upregulated in HCC tissues. It is highly expressed and specific in hepatitis B-related liver cancer. Patients with HCC have high ESPL1 expression level and ESPL1 mutations can lead to poor prognosis. ESPL1 can be used as a potential marker for poor prognosis in patients with HCC.

Key words: Extra spindle poles-like 1 protein, Hepatocellular carcinoma, Hepatitis B, Prognosis

胡伯斌, 王荣明, 梁蘅恺, 韦璐, 黎清梅, 苏土梅, 殷倩冰, 江建宁. ESPL1基因在肝细胞癌组织中的表达及其在预后评估中的作用[J]. 肝脏, 2023, 28(3): 285-289.

HU Bo-bin, WANG Rong-ming, LIANG Heng-kai, WEI Lu, LI Qing-mei, SU Tu-mei, YIN Qian-bing, JIANG Jian-ning. Expression of ESPL1 gene in hepatocellular carcinoma tissue and its role in the prognosis assessment[J]. Chinese Hepatolgy, 2023, 28(3): 285-289.

参考文献

[1] 中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2022年版). 肿瘤防治研究,2022,49(3):251-276.
[2] Bacac M, Fusco C, Planche A, et al. Securin and separase modulate membrane traffic by affecting endosomal acidification. Traffic,2011,12(5):615-626.
[3] Luo S, Tong L. Structural biology of the separase-securin complex with crucial roles in chromosome segregation. Curr Opin Struct Biol,2018,49:114-122.
[4] Shindo N, Otsuki M, Uchida KSK, et al. Prolonged mitosis causes separase deregulation and chromosome nondisjunction. Cell Rep,2021,34(3):108652.
[5] Zhang N, Pati D. Biology and insights into the role of cohesin protease separase in human malignancies. Biol Rev Camb Philos Soc,2017,92(4):2070-2083.
[6] Liu X, Zeng W, Zheng D, et al. Let-7c-5p restrains cell growth and induces apoptosis of lung adenocarcinoma cells via targeting ESPL1. Mol Biotechnol,2022,64(12):1367-1375.
[7] Nie Z, Pu T, Han Z, et al. Extra spindle pole bodies-like 1 serves as a prognostic biomarker and promotes lung adenocarcinoma metastasis. Front Oncol,2022,12:930647.
[8] Buechler SA, Gray KP, Gökmen-Polar Y, et al. Independent validation of early R gene signature in BIG 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer. JNCI Cancer Spectr,2019,3(4):pkz051.
[9] Gurvits N, Löyttyniemi E, Nykänen M, et al. Separase is a marker for prognosis and mitotic activity in breast cancer. Br J Cancer,2017,117(9):1383-1391.
[10] Wang Y, Yang Z. A Gleason score-related outcome model for human prostate cancer: a comprehensive study based on weighted gene co-expression network analysis. Cancer Cell Int,2020,20:159.
[11] Jeong PY, Kumar A, Joshi PM, et al. Intertwined functions of separase and caspase in cell division and programmed cell death. Sci Rep,2020,10(1):6159.
[12] Singleton MR, Uhlmann F. Separase-securin complex: a cunning way to control chromosome segregation. Nat Struct Mol Biol,2017,24(4):337-339.
[13] Wirth KG, Wutz G, Kudo NR, et al. Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression. J Cell Biol,2006,172(6):847-860.
[14] Ruppenthal S, Kleiner H, Nolte F, et al. Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS. PLoS One,2018,13(1):e0191734.
[15] Mukherjee M, Ge G, Zhang N, et al. Separase loss of function cooperates with the loss of p53 in the initiation and progression of T-and B-cell lymphoma, leukemia and aneuploidy in mice. PLoS One,2011,6(7):e22167.
[16] Liu Z, Lian X, Zhang X, et al. ESPL1 is a novel prognostic biomarker associated with the malignant features of glioma. Front Genet,2021,12:666106.
[17] Yang Q, Yu B, Sun J. TTK, CDC25A, and ESPL1 as prognostic biomarkers for endometrial cancer. Biomed Res Int,2020,2020:4625123.
[18] Wang R, Zang W, Hu B, et al. Serum ESPL1 can be used as a biomarker for patients with hepatitis B virus-related liver cancer: a Chinese case-control study. Technol Cancer Res Treat,2020,19:1533033820980785.
[19] Hu B, Huang W, Wang R, et al. High rate of detection of human ESPL1-HBV S fusion gene in patients with HBV-related liver cancer: A Chinese Case-Control Study. Anticancer Res,2020,40(1):245-252.