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
栗英林1,2,宋道庆3,徐忠华1
LI Yinglin1,2, SONG Daoqing3, XU Zhonghua1
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。
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[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, Dangelillo 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. |
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