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胰腺癌中的G蛋白偶联受体激酶2:临床病理及预后意义

G-protein-coupled receptor kinase 2 in pancreatic cancer: clinicopathologic and prognostic significance.

作者信息

Zhou Li, Wang Meng-Yi, Liang Zhi-Yong, Zhou Wei-Xun, You Lei, Pan Bo-Ju, Liao Quan, Zhao Yu-Pei

机构信息

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China.

出版信息

Hum Pathol. 2016 Oct;56:171-7. doi: 10.1016/j.humpath.2016.06.012. Epub 2016 Jun 23.

Abstract

G-protein-coupled receptor kinase 2 (GRK2) was found to regulate biological behaviors in some cancers, including pancreatic cancer (PC). However, its clinicopathologic and prognostic implications in cancer remain unclear. This study was designed to address the issues in PC. Expression of GRK2 was measured by Western blotting and tissue microarray-based immunohistochemical staining in 3 and 171 patients with PC, respectively. The H-score was used to evaluate the staining results. In addition, GRK2 expression was correlated with clinicopathologic variables and overall survival. Finally, the prognostic value of GRK2 was validated in a publically available PC dataset, GSE21501. It was suggested that GRK2 expression was highly up-regulated in 2 out of 3 tumor samples, in contrast to corresponding non-tumor ones. Furthermore, H-score of GRK2 staining was significantly higher in tumor than in non-tumor tissues. Tumoral expression of GRK2 was significantly associated with T stage. Univariate analysis showed that high GRK2 expression in tumor tissues was predictive for poor overall survival of PC. However, GRK2 expression was not identified as an independent prognostic marker in multivariate Cox regression test, although close to the statistical significance. In dataset GSE21501, GRK2 was also revealed to be prognostic. Our data establish that GRK2 is overexpressed in PC, and might serve as a potential indicator of unfavorable prognosis.

摘要

G蛋白偶联受体激酶2(GRK2)被发现可调节包括胰腺癌(PC)在内的某些癌症的生物学行为。然而,其在癌症中的临床病理和预后意义仍不清楚。本研究旨在解决PC中的这些问题。分别通过蛋白质印迹法和基于组织芯片的免疫组化染色检测了3例和171例PC患者的GRK2表达。采用H评分评估染色结果。此外,GRK2表达与临床病理变量及总生存期相关。最后,在公开可用的PC数据集GSE21501中验证了GRK2的预后价值。结果表明,与相应的非肿瘤样本相比,3个肿瘤样本中有2个的GRK2表达高度上调。此外,GRK2染色的H评分在肿瘤组织中显著高于非肿瘤组织。GRK2的肿瘤表达与T分期显著相关。单因素分析显示,肿瘤组织中GRK2高表达预示着PC患者总生存期较差。然而,尽管接近统计学显著性,但在多因素Cox回归分析中GRK2表达未被确定为独立的预后标志物。在数据集GSE21501中,GRK2也显示出具有预后价值。我们的数据表明,GRK2在PC中过度表达,可能是不良预后的潜在指标。

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