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) ›› 2014, Vol. 52 ›› Issue (7): 50-55.doi: 10.6040/j.issn.1671-7554.0.2014.002

• 临床医学 • 上一篇    下一篇

GRK6在胃癌中的表达及其预后价值

张诤, 申洪昌, 付国斌, 张建超, 王潍博   

  1. 山东大学附属省立医院肿瘤科, 山东 济南 250021
  • 收稿日期:2014-01-02 修回日期:2014-06-12 出版日期:2014-07-10 发布日期:2014-07-10
  • 通讯作者: 王潍博。E-mail:wbwb1620@163.com E-mail:wbwb1620@163.com

Expression of GRK6 in gastric carcinoma and its prognostic value

ZHANG Zheng, SHEN Hongchang, FU Guobin, ZHANG Jianchao, WANG Weibo   

  1. Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2014-01-02 Revised:2014-06-12 Online:2014-07-10 Published:2014-07-10

摘要: 目的 通过检测G蛋白偶联受体激酶6(G protein coupled receptor kinase 6, GRK6)在胃癌中的表达情况,探讨其与相关临床病理参数及生存预后的关系。方法 通过组织芯片及免疫组化技术,检测132例胃恶性肿瘤及8例胃良性疾病中GRK6 的表达情况,统计学分析影响GRK6表达情况的相关因素,并根据相关随访资料,探讨GRK6表达与患者预后的关系。结果 GRK6在120例胃恶性肿瘤中高表达率为49.17%,低表达率为50.83%,多因素Logistic回归分析表明GRK6的表达与肿瘤分化相关(P<0.05)。GRK6高表达患者的5年存活率为28.81%,低表达者的5年存活率为67.21%,差异有统计学意义(P<0.05)。Cox生存预后分析提示GRK6的表达及术后有无治疗为影响胃癌患者预后的独立因素(P<0.05)。结论 GRK6在胃腺癌中的表达程度与肿瘤的分化情况密切相关,高表达者的5年生存率明显低于低表达者,为胃癌患者的不良预后指标,可能在胃癌发生发展中起重要作用。

关键词: 组织芯片, 免疫组化, 生存预后, 胃肿瘤, G蛋白偶联受体激酶6

Abstract: Objective To investigate the expression of G protein coupled receptor kinase 6 (GRK6) in gastric carcinoma in order to examine its correlation with the clinicopathologial parameters and prognosis of gastric cancer. Methods GRK6 expressions in 132 malignant gastric carcinoma cases and 8 benign cases were detected with tissue microarray and immunohistochemistry technique. Relevant factors influencing GRK6 expression were analyzed statistically. Association between GRK6 expression and prognosis of gastric cancer was evaluated with reference to follow-up data. Results The high expression rate of GRK6 in gastric carcinoma was 49.17%, and the low expression rate was 50.83%. Multivariate logistic regression analysis disclosed that there was correlation between GRK6 expression and poor differentiation (P<0.05). The 5-year overall survival rates of patients with high and low GRK6 expressions were 28.81% and 67.21%, respectively (P<0.05). Multivariate Cox regression analysis showed that GRK6 was an independent prognostic factor of gastric cancer (P<0.05). Conclusion GRK6 expression in gastric carcinoma is significantly higher than in benign cases. The overexpression of GRK6 is closely correlated with histological differentiation. GRK6 may play an important role in the occurrence and development of gastric carcinoma.

Key words: Stomach neoplasm, Tissue microarray, Prognosis, G protein coupled receptor kinase 6, Immunohistochemistry

中图分类号: 

  • R735.2
[1] Jemal A, Siegel R, Ward E, et al. Cancer statistics 2008[J]. CA Cancer J Clin, 2008, 58(4):71-96.
[2] Roder D M, Kelley J R, Duggan J M. Gastric cancer epidemiology and risk factors[J]. J Clin Epidemiol, 2003, 56(1):1-9.
[3] Pitcher J A, Freedman N J, Lefkowitz R J. G protein-coupled receptor kinases[J]. Annurev Biochem, 1998, 67(1):653-692.
[4] Premont R T. Once and future signaling:G protein-coupled receptor kinase control of neuronal sensitivity[J]. Neuromolecular Med, 2005, 7(1-2):129-147.
[5] Claing A, Laporte S A, Caron M G, et al. Endocytosis of G protein-coupled receptors:roles of G protein-coupled receptor kinases and beta-arrestin proteins[J]. Prog Neurobiol, 2002, 66(2):61-79.
[6] Lymperopoulos A, Bathgate A. Pharmacogenomics of the heptahelical receptor regulators G-protein-coupled receptor kinases and arrestins:the known and the unknown[J]. Pharmacogenomics, 2012, 13(3):323-341.
[7] Raghuwanshi S K, Smith N, Rivers E J, et al. G protein-coupled receptor kinase 6 deficiency promotes angiogenesis, tumor progression, and metastasis[J]. J Immunol, 2013, 190(10):5329-5336.
[8] Tiedemann R E, Zhu Y X, Schmidt J, et al. Kinome-wide RNAi studies in human multiple myeloma identify vulnerable kinase targets, including a lymphoid-restricted kinase, GRK6[J]. Blood, 2010, 115(8):1594-1604.
[9] Li Y P. GRK6 expression in patients with hepatocellular carcinoma[J]. Asian Pac J Trop Med, 2013, 6(3):220-223.
[10] Kononen J, Bubendortf L, Kallioniemi A, et al. Tissue microarrays for high through put molecular profiling of tumor specimens[J]. Nat Med, 1998, 4(7):844-847.
[11] Métayé T, Gibelin H, Perdrisot R, et al. Pathophysiological roles of G-protein-coupled receptor kinases[J]. Cell Signal, 2005, 17(8):917-928.
[12] Hupfeld C J, Olefsky J M. Regulation of receptor tyrosine kinase signaling by GRKs and beta-arrestins[J]. Annu Rev Physiol, 2007, 69:561-577.
[13] Cipolletta E, Campanile A, Santulli G, et al. The G protein coupled receptor kinase 2 plays an essential role in beta-adrenergic receptor-induced insulin resistance[J]. Cardiovasc Res, 2009, 84(3):407-415.
[14] Penela P, Murga C, Ribas C, et al. The complex G protein-coupled receptor kinase 2 (GRK2) interactome unveils new physiopathological targets[J]. Br J Pharmacol, 2010, 160(4):821-832.
[15] Martini J S, Raake P, Vinge L E, et al. Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes[J]. Proc Natl Acad Sci USA, 2008, 105(34) :12457-12462.
[16] Woerner B M, Luo J, Brown K R, et al. Suppression of G-protein-coupled receptor kinase 3 expression is a feature of classical GBM that is required for maximal growth[J]. Mol Cancer Res, 2012, 10(1):156-166.
[17] Métayé T, Menet E, Guilhot J, et al. Expression and activity of G protein-coupled receptor kinases in differentiated thyroid carcinoma[J]. J Clin Endocrinol Metab, 2002, 87(7):3279-3286.
[18] Kim J I, Chakraborty P, Wang Z, et al. G-protein coupled receptor kinase 5 regulates prostate tumor growth[J]. J Urol, 2012, 187(1):322-329.
[19] Wu C C, Tsai F M, Shyu R Y, et al. G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells[J]. BMC Cancer, 2011, 11:175. doi:10.1186/1471-2407-11-175.
[20] Wei Z, Hurtt R, Ciccarelli M, et al. Growth inhibition of human hepatocellular carcinoma cells by overexpression of G protein-coupled receptor kinase2[J]. J Cell Physiol, 2012, 227(6):2371-2377.
[1] 底学敏,牛书雷,赵静,杜随,于慧敏,张宏涛,王娟. CT引导下125I粒子植入治疗晚期胃癌淋巴结转移[J]. 山东大学学报(医学版), 2017, 55(9): 79-84.
[2] 聂思月,王震,孙靖宇,刘杰,李娟,魏小娟,路春晓,吕兴龑,王淑云,孙玉萍. ANGPTL5在人胃癌组织中的表达及临床意义[J]. 山东大学学报(医学版), 2017, 55(8): 61-65.
[3] 贾振军, 曲勇, 张世杰. HER2和p53在胃腺癌不同衍变阶段中的表达及意义[J]. 山东大学学报(医学版), 2015, 53(3): 73-76.
[4] 丁娟, 郑桂喜, 杜鲁涛, 尹作花, 张建, 王传新. 外周血sHLA-G与PGR、GPR联合检测在胃癌诊断中的效能评估[J]. 山东大学学报(医学版), 2015, 53(11): 59-63.
[5] 徐翠, 王涛, 周平. 儿童幽门螺杆菌免疫组化染色检测分析[J]. 山东大学学报(医学版), 2014, 52(9): 81-84.
[6] 许加军, 刘宗现, 许风雷, 王磊, 孔维华. 自噬相关蛋白4EBP1与eIF4E在几种常见脑瘤组织中的表达[J]. 山东大学学报(医学版), 2014, 52(9): 72-76.
[7] 李玲, 王丽丽, 王胜江, 于超, 刘延鹏, 徐成伟. 乳腺癌患者血浆D-二聚体水平与预后关系的探讨[J]. 山东大学学报(医学版), 2014, 52(9): 77-80.
[8] 连海峰, 李明, 刘成霞, 贾兴芳, 李丹. NRP2在胃癌中的表达及其临床意义[J]. 山东大学学报(医学版), 2014, 52(7): 56-59.
[9] 赵华1,徐洋洋2,鹿向东3,徐同江1 . Ki-67、PTTG、VEGF与垂体瘤卒中的相关性[J]. 山东大学学报(医学版), 2014, 52(5): 82-85.
[10] 胡瑞1,郏雁飞2,郑燕2,马晓丽2,孔毅1,黎娉1,汪运山2. 缺氧对人胃癌细胞HIF-1α及DEC1表达的影响[J]. 山东大学学报(医学版), 2014, 52(4): 35-38.
[11] 王晓蕾1,郏雁飞2,郑燕2,刘华2,汪运山2. STAT3真核表达质粒的构建及对胃癌细胞增殖的影响[J]. 山东大学学报(医学版), 2013, 51(9): 45-49.
[12] 樊明德1,张源2,苗保旺1,郑鲲鹏1,李科1,王成伟1. Nod样受体热蛋白结构域相关蛋白3在人脑胶质瘤中的表达[J]. 山东大学学报(医学版), 2013, 51(4): 51-54.
[13] 邢海燕1,2,薛凤华3,秦晓敏4,张建平1,4. HIF-1α、VEGF和MMP-9在子宫内膜样腺癌中的表达及临床意义[J]. 山东大学学报(医学版), 2013, 51(4): 77-80.
[14] 王臣臣1,顾晓萌1,王妍2,黄山英3 . TFF3在胃癌、癌前病变中的表达及与血管生成的关系[J]. 山东大学学报(医学版), 2013, 51(2): 99-103.
[15] 刘海燕1,李陪2,高辉3,朱长军2,董智雄2. 染色体驱动蛋白KIF4A对胃癌细胞迁移和转移的影响[J]. 山东大学学报(医学版), 2013, 51(12): 25-28.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!