您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (9): 45-51.doi: 10.6040/j.issn.1671-7554.0.2020.0367

• • 上一篇    下一篇

应用生物信息学方法分析肾透明细胞癌中FKBP11的表达

栗英林1,2,宋道庆3,徐忠华1   

  1. 1. 山东大学齐鲁医院泌尿外科, 山东 济南 250012;2. 冠县人民医院泌尿外科, 山东 冠县 252500;3. 昆山市康复医院泌尿外科, 江苏 昆山 215300
  • 出版日期:2020-09-10 发布日期:2020-08-30
  • 通讯作者: 徐忠华. E-mail:xuzhonghua1963@163.com

Identification of FKBP11 expression in clear cell renal cell carcinoma using bioinformatics analysis

LI Yinglin1,2, SONG Daoqing3, XU Zhonghua1   

  1. 1. Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Department of Urology, Gunxian Peoples Hospital, Guanxian 252500, Shandong, China;
    3. Department of Urology, Kunshan Rehabilitation Hospital, Kunshan 215300, Jiangsu, China
  • Online:2020-09-10 Published:2020-08-30

摘要: 目的 探讨FK506结合蛋白11(FKBP11)在肾透明细胞癌(ccRCC)中的表达,并分析FKBP11表达水平与患者临床病理特征之间的相关性。 方法 利用Ualcan、GEPIA 数据库和HPA数据库分析FKBP11在ccRCC 组织中mRNA和蛋白表达水平的变化、FKBP11表达与ccRCC 临床及病理特征的相关性及其对患者预后的影响,通过这几个维度分析FKBP11在ccRCC中的作用。 结果 FKBP11在ccRCC中mRNA的表达较正常肾组织升高,通过Ualcan数据库检测发现FKBP11在ccRCC病理分级中正常肾组织与Grade1、Grade2、Grade3、Grade4中表达差异分别为P=5.78E-05、P=1.62E-12、P=1.11E-16、P=1.63E-12,在ccRCC亚型(ccA和ccB)中正常与ccA及ccB中表达差异均为P=1.62E-12, TNM分期中正常与N0及N1分期各亚组之间的表达有差异(P<1E-12、P=8.26E-05),以上差异均具有统计学意义(P<0.05),且随着ccRCC病理分级的升高,FKBP11的表达存在上调趋势,其表达水平与ccRCC的进展相关,而FKBP11的表达水平与年龄、性别、人种各亚组之间相互比较差异均无统计学意义(P>0.05)。FKBP11高表达患者的总生存率较低表达组患者差异有统计学意义(P<0.01)。 结论 通过检索分析数据库信息发现FKBP11在ccRCC中呈高表达,其在ccRCC的不同分期、病理分级及亚型各亚组之间存在表达差异,较差的病理分级及分期FKBP11的表达较高,且高表达的FKBP11的ccRCC患者预后较差。

关键词: FK506结合蛋白11, 肾透明细胞癌, 生物信息学, 预后

Abstract: Objective To explore the expression of FK506 binding protein 11(FKBP11)in clear cell renal cell carcinoma(ccRCC), and to analyze its correlation with the clinicopathological features of ccRCC. Methods Based on Ualcan, GEPIA and HPA databases, the mRNA and protein expressions of FKBP11 in ccRCC, their correlation with the clinicopathological features of ccRCC, and their effects on the prognosis of patients were analyzed. Results The mRNA expression of FKBP11 was higher in ccRCC tissues than in normal kidney tissues. Analysis of Ualcan database showed differences in FKBP11 expression between normal kidney tissues and Grade 1(P=5.78E-051), Grade 2(P=1.62E-12), Grade 3(P=1.11E-16)and Grade 4(P=1.63E-12)ccRCC. The expression differences between normal and ccA and ccB subtypes were both P=1.62E-12. There were differences between normal and N0(P<1E-12)and N1(P=8.26E-05)subtypes in TNM staging. With higher ccRCC pathological grading, the expression of FKBP11 was up-regulated and related to the progression of ccRCC. However, there were no differences among different age, sex and race groups(P>0.05). There was difference in the overall survival rate between patients with high and low expressions of FKBP11(P<0.01). Conclusion Bioinformatics analysis indicated that FKBP11 was highly expressed in ccRCC, and there were differences in FKBP11 expressions among different stages, pathological grades and subtypes of ccRCC. Poorer pathological grades and stages of ccRCC showed higher expression of FKBP11, and high expression of FKBP11 indicated poorer prognosis.

Key words: FK506-binding protein-11, Clear cell renal cell carcinoma, Bioinformatics, Prognosis

中图分类号: 

  • R737.11
[1] Barata PC, Rini BI. Treatment of renal cell carcinoma: current status and future directions [J]. CA Cancer J Clin, 2017, 67(6): 507-524.
[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017 [J]. CA Cancer J Clin, 2017, 67(1): 7-30.
[3] Ge Y, Xu A, Zhang M, et al. FK506 binding protein 10 is overexpressed and promotes renal cell carcinoma [J]. Urol Int, 2017, 98(2): 169-176.
[4] Yang WS, Moon HG, Kim HS, et al. Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer [J]. J Proteome Res, 2012, 11(2): 1078-1088.
[5] Knuppel L, Heinzelmann K, Lindner M, et al. FK506-binding protein 10(FKBP10)regulates lung fibroblast migration via collagen VI synthesis [J]. Respir Res, 2018, 19(1): 67. doi: 10.1186/s12931-018-0768-1.
[6] Romano S, Staibano S, Greco A, et al. FK506 binding protein 51 positively regulates melanoma stemness and metastatic potential [J]. Cell Death Dis, 2013, 4(4): e578. doi: 10.1038/cddis.2013.109.
[7] Wang RG, Zhang D, Zhao CH, et al. FKBP10 functioned as a cancer-promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma [J]. Kaohsiung J Med Sci, 2020, 36(5): 311-317.
[8] Daudt DR, Yorio T. FKBP51 protects 661w cell culture from staurosporine-induced apoptosis [J]. Mol Vis, 2011, 17:1172-1181. Epub 2011 May 4.
[9] Romano S, Dangelillo A, Staibano S, et al. FK506-binding protein 51 is a possible novel tumoral marker [J]. Cell Death Dis, 2010, 1(7): e55. doi: 10.1038/cddis.2010.32.
[10] Lin IY, Yen CH, Liao YJ, et al. Identification of FKBP11 as a biomarker for hepatocellular carcinoma [J]. Anticancer Res, 2013, 33(6): 2763-2769.
[11] Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses [J]. Neoplasia, 2017, 19(8): 649-658.
[12] 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, 2017,45(W1): W98-W102.
[13] Thul PJ, Lindskog C. The human protein atlas: a spatial map of the human proteome [J]. Protein Sci, 2018, 27(1): 233-244.
[14] Lipworth L, Tarone RE, Mclaughlin JK. The epidemiology of renal cell carcinoma [J]. J Urol, 2006, 176(6 Pt 1): 2353-2358.
[15] Flanigan RC, Campbell SC, Clark JI, et al. Metastatic renal cell carcinoma [J]. Curr Treat Options Oncol, 2003, 4(5): 385-390.
[16] 魏先, 胡志全. 转移性肾细胞癌免疫治疗进展[J]. 现代泌尿生殖肿瘤杂志, 2017, 9(1): 1-4.
[17] Motzer RJ, Escudier B, Oudard S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors [J]. Cancer, 2010, 116(18): 4256-4265.
[18] Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial [J]. J Clin Oncol, 2010, 28(6): 1061-1068.
[19] Ramadori G, Ioris RM, Villanyi Z, et al. FKBP10 Regulates Protein Translation to Sustain Lung Cancer Growth [J]. Cell Rep, 2020, 30(11): 3851-3863.
[20] Brebi P, Maldonado L, Noordhuis MG, et al. Genome-wide methylation profiling reveals Zinc finger protein 516(ZNF516)and FK-506-binding protein 6(FKBP6)promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population [J]. Epigenetics, 2014, 9(2): 308-317.
[21] Yao YL, Liang YC, Huang HH, et al. FKBPs in chromatin modification and cancer [J]. Curr Opin Pharmacol, 2011, 11(4): 301-307.
[22] Chen YG, Liu F, Massague J. Mechanism of TGFbeta receptor inhibition by FKBP12 [J]. EMBO J, 1997, 16(13): 3866-3876.
[23] Xu X, Su B, Barndt RJ, et al. FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506 [J]. Transplantation, 2002, 73(11): 1835-1838.
[24] Fan G, Yang Y, Li T, et al. A Phytophthora capsici RXLR Effector Targets and Inhibits a Plant PPIase to Suppress Endoplasmic Reticulum-Mediated Immunity [J]. Mol Plant, 2018, 11(8): 1067-1083.
[25] Chen H, Zhang W, Sun X, et al. Fkbp1a controls ventricular myocardium trabeculation and compaction by regulating endocardial Notch1 activity [J]. Development, 2013, 140(9): 1946-1957.
[26] Lietman CD, Lim J, Grafe I, et al. Fkbp10 deletion in osteoblasts leads to qualitative defects in bone [J]. J Bone Miner Res, 2017, 32(6): 1354-1367.
[27] Liu FL, Liu TY, Kung FL. FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines [J]. J Biosci, 2014, 39(1): 85-95.
[28] Chambraud B, Sardin E, Giustiniani J, et al. A role for FKBP52 in Tau protein function [J]. Proc Natl Acad Sci U S A, 2010, 107(6): 2658-2663.
[29] Rulten SL, Kinloch RA, Tateossian H, et al. The human FK506-binding proteins: characterization of human FKBP19 [J]. Mamm Genome, 2006, 17(4): 322-331.
[30] Zhang K, Wang S, Malhotra J, et al. The unfolded protein response transducer IRE1alpha prevents ER stress-induced hepatic steatosis [J]. EMBO J, 2011, 30(7): 1357-1375.
[31] Lu H, Yang Y, Allister EM, et al. The identification of potential factors associated with the development of type 2 diabetes: a quantitative proteomics approach [J]. Mol Cell Proteomics, 2008, 7(8): 1434-1451.
[32] Ruer-Laventie J, Simoni L, Schickel JN, et al. Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation[J]. Immun Inflamm Dis, 2015, 3(3): 265-279.
[1] 史爽,李娟,米琦,王允山,杜鲁涛,王传新. 胃癌miRNAs预后风险评分模型的构建与应用[J]. 山东大学学报 (医学版), 2020, 58(7): 47-52.
[2] 罗昕,何兵,聂清生,侯震波,董军,李玉花,曾祥芹,刘伟,孔德民,曹金凤. 磁共振扩散加权成像单指数模型与扩散峰度成像模型在61例肾透明细胞癌分级中的对比[J]. 山东大学学报 (医学版), 2020, 58(7): 89-95.
[3] 路璐,孙志钢,张楠. 继发性嗜血细胞综合征1例[J]. 山东大学学报 (医学版), 2020, 58(7): 122-124.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!