抗凋亡转录因子在肝细胞肝癌中的表达及预后作用

doi:10.6040/j.issn.1671-7554.0.2018.463

摘要/Abstract

摘要： 目的分析抗凋亡转录因子(AATF)在肝细胞肝癌(LIHC)中的表达及意义。方法分别利用基因表达谱交互式分析(GEPIA)和人类蛋白质图谱(HPA)分析AATF mRNA与蛋白在肝细胞肝癌(LIHC)组织及对照组织的差异表达及定位;通过cBioPortal分析AATF在LIHC基因组改变及与AATF相互作用的蛋白质网络;通过Kaplan-Meier Plotter分析AATF对肝癌患者5年生存期及总生存期的影响;通过Tumor Immune Estimation Resource分析AATF与LIHC患者生存期的相关性。结果与对照组织相比,AATF的mRNA(P<0.05)及蛋白表达水平在LIHC组织中显著上调,其蛋白在两种组织的细胞膜及细胞质中均有定位。AATF的基因组改变在LIHC中发生率很低。与AATF相互作用的蛋白有ATM丝氨酸/苏氨酸激酶、检查点激酶2(CHEK2)等,主要参与调控细胞周期、细胞凋亡及转录调控等过程。AATF mRNA表达水平与LIHC患者的预后呈负相关(log-rank P=0.003)。结论 AATF在LIHC组织中高表达,且与患者不良预后相关。

关键词: 抗凋亡转录因子, 肝细胞肝癌, 预后, 数据分析

Abstract: Objective To analyze the expression and prognostic significance of apoptosis antagonizing transcription factor(AATF)in liver hepatocellular carcinoma(LIHC). Methods The mRNA and protein expressions and location of AATF in LIHC tissues and control tissues were detected with GEPIA and the Human Protein Atlas. The genomic alterations of AATF in LIHC tissues and the protein network diagram associated with AATF protein were assessed with cBioPortal. The effects of AATF on the 5-year survival and overall survival of liver cancer patients were determined with Kaplan-Meier Plotter. The prognostic significance of AATF in LIHC patients was analyzed with Tumor Immune Estimation Resource. Results Compared with the control tissues, the LIHC tissues showed significantly up-regulated mRNA(P<0.05)and protein expressions of AATF. AATF protein was located in the membrane and cytoplasm of LIHC cells. The genomic alterations of AATF had a low incidence in LIHC. The proteins that interacted with AATF included ATM, CHEK2, and so on, which were mainly involved in the regulation of cell cycle, apoptosis, and transcriptional regula- 山东大学学报 (医学版)56卷12期 -邵倩倩,等. 抗凋亡转录因子在肝细胞肝癌中的表达及预后作用 \=-tion. The mRNA expression of AATF was negatively correlated with the prognosis of LIHC(log-rank P=0.003). Conclusion AATF is highly expressed in LIHC tissues and associated with poor prognosis.

Key words: Apoptosis antagonizing transcription factor, Liver hepatocellular carcinoma, Prognosis, Data analysis

中图分类号:

R735.7

邵倩倩,王景溥,王庆杰. 抗凋亡转录因子在肝细胞肝癌中的表达及预后作用[J]. 山东大学学报 (医学版), 2018, 56(12): 7-12.

SHAO Qianqian, WANG Jingpu, WANG Qingjie. Expression and prognostic significance of apoptosis antagonizing transcription factor in hepatocellular carcinoma[J]. Journal of Shandong University (Health Sciences), 2018, 56(12): 7-12.

参考文献

[1] Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma[J]. Lancet, 2012, 379(9822): 1245-1255.
[2] Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives[J]. Gut, 2014, 63(5): 844-855.
[3] Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005[J]. J Clin Oncol, 2009, 27(9): 1485-1491.
[4] Lindfors K, Halttunen T, Huotari P, et al. Identification of novel transcription factor-like gene from human intestinal cells[J]. Biochem Biophys Res Commun, 2000, 276(2): 660-666.
[5] Bruno T, Iezzi S, Fanciulli M. Che-1/AATF: a critical cofactor for both wild-Type- and mutant-p53 proteins[J]. Front Oncol, 2016, 6: 34. doi: 10.3389/fonc.2016.00034.
[6] Di Padova M, Bruno T, De Nicola F, et al. Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter[J]. J Biol Chem, 2003, 278(38): 36496-36504.
[7] Hopker K, Hagmann H, Khurshid S, et al. AATF/Che-1 acts as a phosphorylation-dependent molecular modulator to repress p53-driven apoptosis[J]. EMBO J, 2012, 31(20): 3961-3975.
[8] Desantis A, Bruno T, Catena V, et al. Che-1-induced inhibition of mTOR pathway enables stress-induced autophagy[J]. EMBO J, 2015, 34(9): 1214-1230.
[9] Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses[J]. Nucleic Acids Res, 2017, 3(45 W1): W98-W102. doi: 10.1093/nar/gkx247.
[10] Uhlen M, Oksvold P, Fagerberg L, et al. Towards a knowledge-based Human Protein Atlas[J]. Nat Biotechnol, 2010, 28(12): 1248-1250.
[11] Uhlen M, Fagerberg L, Hallstrom BM, et al. Proteomics. Tissue-based map of the human proteome[J]. Science, 2015, 347(6220): 1260419. doi: 10.1126/science.1260419.
[12] Uhlen M, Zhang C, Lee S, et al. A pathology atlas of the human cancer transcriptome[J]. Science, 2017, 357(6352): pii: eaan2507. doi: 10.1126/science.aan2507.
[13] Thul PJ, Akesson L, Wiking M, et al. A subcellular map of the human proteome[J]. Science, 2017, 356(6340): pii: eaal3321. doi: 10.1126/science.aal3321.
[14] Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data[J]. Cancer Discov, 2012, 2(5): 401-404.
[15] Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal[J]. Sci Signal, 2013, 6(269): pl1. doi: 10.1126/scisignal.2004088.
[16] Szasz AM, Lanczky A, Nagy A, et al. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients[J]. Oncotarget, 2016, 7(31): 49322-49333.
[17] Li B, Severson E, Pignon JC, et al. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy[J]. Genome Biol, 2016, 17(1): 174.
[18] Li T, Fan J, Wang B, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells[J]. Cancer Res, 2017, 77(21): e108-e110. doi: 10.1158/0008-5472.CAN-17-0307.
[19] Liu H, Yang C, Lu W, et al. Prognostic significance of glypican-3 expression in hepatocellular carcinoma: a meta-analysis[J]. Medicine(Baltimore), 2018, 97(4): e9702. doi: 10.1097/MD.0000000000009702.
[20] Miki D, Ochi H, Hayes CN, et al. Hepatocellular carcinoma: towards personalized medicine[J]. Cancer Sci, 2012, 103(5): 846-850.
[21] Berger AC, Korkut A, Kanchi RS, et al. A comprehensive pan-cancer molecular study of gynecologic and breast cancers[J]. Cancer Cell, 2018, 33(4): 690-705.e9. doi: 10.1016/j.ccell.2018.03.014.
[22] Liu J, Lichtenberg T, Hoadley KA, et al. An integrated TCGA Pan-cancer clinical data resource to drive high-quality survival outcome analytics[J]. Cell, 2018, 173(2): 400-416. e11. doi: 10.1016/j.cell.2018.02.052.
[23] Passananti C, Floridi A, Fanciulli M. Che-1/AATF, a multivalent adaptor connecting transcriptional regulation, checkpoint control, and apoptosis[J]. Biochem Cell Biol, 2007, 85(4): 477-483.
[24] Passananti C, Fanciulli M. The anti-apoptotic factor Che-1/AATF links transcriptional regulation, cell cycle control, and DNA damage response[J]. Cell Div, 2007, 2: 21. doi: 10.1186/1747-1028-2-21.
[25] Di Certo MG, Corbi N, Bruno T, et al. NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death[J]. J Cell Sci, 2007, 120(Pt 11): 1852-1858.
[26] Fanciulli M, Bruno T, Di Padova M, et al. Identification of a novel partner of RNA polymerase II subunit 11, Che-1, which interacts with and affects the growth suppression function of Rb[J]. FASEB J, 2000, 14(7): 904-912.
[27] Bruno T, De Angelis R, De Nicola F, et al. Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb[J]. Cancer Cell, 2002, 2(5): 387-399.
[28] Jackson JG,Lozano G. Che-ating death: CHE1/AATF protects from p53-mediated apoptosis[J]. EMBO J, 2012, 31(20): 3951-3953.

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