SUB1在肝癌患者中的预后价值

doi:10.3969/j.issn.1009-976X.2020.04.004

摘要/Abstract

摘要： 目的利用TCGA及Oncomine数据库,分析SUB1在肝癌组织中的表达水平;评价SUB1在肝癌患者中的预后价值;利用基因集富集分析（GSEA）及及基因集变异分析（GSVA）分析受SUB1影响的细胞通路。方法下载TCGA的肝癌队列RNA-seq数据,通过质量控制及标准化后分析其在肝癌组织及癌旁的表达变化,进一步在Oncomine数据库中进行分析验证;根据SUB1中位数表达量将TCGA数据库肝癌队列患者分为高表达及低表达两组,进行总生存（OS）分析及无复发生存（RFS）分析;GSEA及GSVA方法用于分析受SUB1调控的细胞通路。结果 SUB1在肝癌组织中的表达高于癌旁组织,P<0.0001;高表达SUB1的肝癌患者OS及RFS均低于低表达SUB1的肝癌患者;高表达SUB1可激活细胞周期、DNA复制等细胞通路。结论 SUB1在肝癌组织中高表达, SUB1可以作为肝癌患者总体生存和无病生存的预后因素。SUB1高表达激活了DNA复制及细胞周期等细胞通路。

关键词: SUB1, 预后, 肝癌, TCGA, Oncomine

Abstract: Objective To analysis the expression levels of SUB1 in liver cancer by using TCGA and Oncomine database; then to evaluate the prognostic value of SUB1 in liver cancer patients; finally to analysis the cell pathways affected by SUB1 by applying Gene Set Enrichment Analysis （GSEA） and Gene Set Variation Analysis （GSVA）. Methods The RNA-seq data of liver cancer cohort were retrieved from TCGA database and the quality control and standardization proceed were implement next, the expression levels of SUB1 were contrasted in liver cancer tissues with adjacent tumors and also further analyzed and verified in the Oncomine database. The patients of liver cancer retrieved from TCGA database were divided into High expression SUB1 group and Low expression SUB1 group according to the median expression of SUB1, then overall survival （OS） analysis and relapse-free survival （RFS） analysis were performed; the methods of GSEA and GSVA were used to analyze the cell pathways regulated by SUB1. Results The expression of SUB1 in liver cancer tissues is higher than that in adjacent tissues, P<0.0001; liver cancer patients with high expression of SUB1 have lower OS and RFS than those patients with low expression of SUB1; high expression of SUB1 can activate cell cycle, DNA replication and other cell pathways. Conclusion SUB1 is highly expressed in liver cancer tissues, and SUB1 can be used as a prognostic marker for overall survival and disease-free survival in liver cancer patients. High expression of SUB1 activates cellular pathways such as DNA replication and cell cycle.

Key words: TCGA, liver cancer, Oncomine, SUB1, Prognostic value

中图分类号:

R735.7

黄勇平, 唐德钧, 刘冬, 张环, 唐光华, 都敏, 杨小兰. SUB1在肝癌患者中的预后价值[J]. 岭南现代临床外科, 2020, 20(04): 425-430.

HUANG Yong-ping, TANG De-jun, LIU Dong, ZHANG Huan, TANG Guang-hua, DU Min, YANG Xiao-lan. Prognostic value of SUB1 in liver cancer patients[J]. Lingnan Modern Clinics in Surgery, 2020, 20(04): 425-430.

参考文献

[1] Ferlay J, Shin H-R, Bray F, et al.Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008[J]. Int J Cancer, 2010, 127(12): 2893-2917.
[2] Torre LA, Bray F, Siegel RL, et al.Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[3] Dang H, Takai A, Forgues M, et al.Oncogenic activation of the RNA binding protein NELFE and MYC signaling in hepatocellular carcinoma[J]. Cancer Cell, 2017, 32(1): 101-114.
[4] Conesa C, Acker J.Sub1/PC4 a chromatin associated protein with multiple functions in transcription[J]. RNA Biol, 2010, 7(3): 287-290.
[5] Das C, Gadad SS, Kundu TK.Human Positive Coactivator 4 Controls Heterochromatinization and Silencing of Neural Gene Expression by Interacting with REST/NRSF and CoREST[J]. J Mol Biol, 2010, 397(1): 1-12.
[6] Kershnar E, Wu SY, Chiang CM.Immunoaffinity purification and functional characterization of human transcription factor IIH and RNA polymerase II from clonal cell lines that conditionally express epitope-tagged subunits of the multiprotein complexes[J]. J Biol Chem, 1998, 273(51): 34444-34453.
[7] Tao S, Yu J, Xu Y, et al.PC4 induces lymphangiogenesis dependent VEGF-C/VEGF-D/VEGFR-3 axis activation in lung adenocarcinoma[J]. Am J Cancer Res, 2015, 5(6): 1878-1889.
[8] Chakravarthi BV, Goswami MT, Pathi SS, et al.MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer[J]. Oncogene, 2016, 35(49): 6330-6340.
[9] Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters[J].OMICS, 2012, 16(5): 284-287.
[10] Hänzelmann S, Castelo R, Guinney J.GSVA: gene set variation analysis for microarray and RNA-Seq data[J]. BMC Bioinformatics, 2013, 14(1): 7.
[11] Kretzschmar M, Kaiser K, Lottspeich F, et al.A novel mediator of class II gene transcription with homology to viral immediate-early transcriptional regulators[J]. Cell, 1994, 78(3): 525-534.
[12] Sato N, Fukushima N, Maitra A, et al.Gene expression profiling identifies genes associated with invasive intraductal papillary mucinous neoplasms of the pancreas[J]. J Clin Pathol, 2004, 164(3): 903-914.
[13] Rhodes DR, Yu J, Shanker K, et al.ONCOMINE: a cancer microarray database and integrated data-mining platform[J]. Neoplasia, 2004, 6(1): 1-6.
[14] Qian D, Zhang B, Zeng XL, et al.Inhibition of human positive cofactor 4 radiosensitizes human esophageal squmaous cell carcinoma cells by suppressing XLF-mediated nonhomologous end joining[J]. Cell Death Dis, 2014, 5(10): e1461.
[15] Chen L, Du C, Wang L, et al.Human positive coactivator 4 (PC4) is involved in the progression and prognosis of astrocytoma[J]. J Neurol Sci, 2014, 346(1): 293-298.