山东大学学报 (医学版) ›› 2020, Vol. 1 ›› 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。
中图分类号:
| [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. |
| [1] | 张秋萍,朱慧志,吕川,夏咏琪,张秀. 基于生物信息学分析鉴定哮喘潜在的关键自噬和铁死亡相关基因[J]. 山东大学学报 (医学版), 2026, 64(1): 74-87. |
| [2] | 李梓绮,魏闫若雪,刘晓晗,刘春铖,赵然,刘玉昆. 长链非编码RNA HEATR3反义RNA 1参与结直肠癌发生发展的功能及其临床意义[J]. 山东大学学报 (医学版), 2025, 63(9): 108-115. |
| [3] | 刘保国,宋翔,赵晓文,毛亚丽. 血清STAT5B、NKAIN1 mRNA检测在乳腺癌中的应用价值[J]. 山东大学学报 (医学版), 2025, 63(7): 68-74. |
| [4] | 王磊,常霄,王梓萌,李娇娇,崔书君,杨飞,朱月香. 瘤内及瘤周DCE-MRI影像组学对宫颈癌患者无进展生存期的预测价值[J]. 山东大学学报 (医学版), 2025, 63(6): 45-54. |
| [5] | 贾若曦,吕丽,刘涵云,吴寅平,李凤彩,赵泽华,王凯,范玉琛. 血细胞计数相关标志物对慢加急性乙型肝炎肝衰竭患者28天预后的诊断价值[J]. 山东大学学报 (医学版), 2025, 63(6): 89-99. |
| [6] | 杜雪,李春霞,刘云霞,张涛. 基于MFPC-Cox的结直肠癌患者预后动态预测模型[J]. 山东大学学报 (医学版), 2025, 63(5): 101-110. |
| [7] | 杨卫芳,徐宏,刘元涛,赵蕙琛. 促甲状腺激素受体抗体在Graves病复发中的作用机制及其临床意义[J]. 山东大学学报 (医学版), 2025, 63(4): 116-121. |
| [8] | 刘文钊,张远,马湘萍,魏峰涛,卜培莉. 内皮活化和应激指数预测值与心力衰竭患者死亡风险的关联[J]. 山东大学学报 (医学版), 2025, 63(11): 27-35. |
| [9] | 陈文亮,王欢欢,郝金锦,弓蕊,赵强,张飞,高磊,董静逊. lncRNA PVT1表达在胃癌预后评估及恶性进展中的作用:基于列线图模型与细胞功能实验的研究[J]. 山东大学学报 (医学版), 2025, 63(10): 61-71. |
| [10] | 王静,刘晓菲,曾荣,许长娟,张锦涛,董亮. 基于机器学习算法鉴定哮喘的坏死性凋亡相关生物标志物[J]. 山东大学学报 (医学版), 2024, 62(7): 21-32. |
| [11] | 郭姝画,樊扬,田风,王传新,杜鲁涛,李培龙,郭兴,徐硕. 微原纤维相关蛋白3在调控胶质瘤干细胞间充质表型转化中的作用[J]. 山东大学学报 (医学版), 2024, 62(6): 9-16. |
| [12] | 魏闫若雪,李梓绮,刘春铖,刘晓晗,赵然,刘玉昆. 结直肠癌中SP1的瘤内异质性表达及其临床意义[J]. 山东大学学报 (医学版), 2024, 62(5): 89-94. |
| [13] | 刘春铖,刘晓晗,魏闫若雪,李梓绮,刘玉昆,赵然. 结直肠癌中含溴结构域蛋白9的亚细胞定位模式及其临床意义[J]. 山东大学学报 (医学版), 2024, 62(4): 24-30. |
| [14] | 杨雪彦,吴寅平,吕丽,赵泽华,马行宇,李凤彩,王凯,范玉琛. 单核细胞与淋巴细胞比值动态变化对慢加急性乙型肝炎肝衰竭预后的诊断价值[J]. 山东大学学报 (医学版), 2024, 62(3): 61-69. |
| [15] | 刁玉洁,林琳,李文瑄,王洲洋,江蓓,胡迎迎,刘广义. NPR预测ANCA相关血管炎不良肾脏预后及其协同多因素优化模型[J]. 山东大学学报 (医学版), 2024, 62(2): 60-68. |
|
||