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GRK2和IGF1R在肝细胞癌中的表达:临床病理及预后意义

Expression of GRK2 and IGF1R in hepatocellular carcinoma: clinicopathological and prognostic significance.

作者信息

Lin Song-Bai, Zhou Li, Liang Zhi-Yong, Zhou Wei-Xun, Jin Ye

机构信息

International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.

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

出版信息

J Clin Pathol. 2017 Sep;70(9):754-759. doi: 10.1136/jclinpath-2016-203998. Epub 2017 Feb 15.

Abstract

AIM

It has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinicopathological and prognostic significance of GRK2 and IGF1R in HCC.

METHODS

Expression of GRK2 and IGF1R was first detected by tissue microarray-based immunohistochemistry in 156 patients with HCC. Staining results, termed the H-score, were then correlated with clinicopathological variables and patient survival. Finally, the prognostic value of GRK2 and IGF1R was validated in the publically available TCGA (The Cancer Genome Atlas) RNA-sequencing database.

RESULTS

The H-score of GRK2 staining (which was significantly lower in tumour than non-tumour tissue) was negatively associated with that of IGF1R with a reverse trend. No clinicopathological significance of the proteins was found except for a relationship between tumoral IGF1R expression and tumour-node-metastasis stage. In univariate analysis, high IGF1R expression predicted poor overall and disease-free survival, whereas GRK2 was not prognostic. In multivariate analysis, IGF1R was significant for overall survival. Furthermore, IGF1R was also of prognostic value in the TCGA database.

CONCLUSIONS

Our data indicate that GRK2 and IGF1R show a negative correlation in HCC. IGF1R could be a potential marker of poor prognosis for this malignancy.

摘要

目的

研究表明,G蛋白偶联受体激酶2(GRK2)对肝细胞癌(HCC)中的胰岛素样生长因子1受体(IGF1R)信号通路具有负向调节作用。本研究旨在评估GRK2和IGF1R在HCC中的临床病理及预后意义。

方法

首先通过基于组织芯片的免疫组化法检测156例HCC患者中GRK2和IGF1R的表达。然后将染色结果(即H评分)与临床病理变量及患者生存率进行关联分析。最后,在公开可用的癌症基因组图谱(TCGA)RNA测序数据库中验证GRK2和IGF1R的预后价值。

结果

GRK2染色的H评分(肿瘤组织中的该评分显著低于非肿瘤组织)与IGF1R的H评分呈负相关,趋势相反。除肿瘤IGF1R表达与肿瘤-淋巴结-转移分期之间的关系外,未发现这些蛋白具有临床病理意义。单因素分析显示,高IGF1R表达预示总体生存率和无病生存率较差,而GRK2无预后价值。多因素分析表明,IGF1R对总体生存率具有显著意义。此外,IGF1R在TCGA数据库中也具有预后价值。

结论

我们的数据表明,GRK2和IGF1R在HCC中呈负相关。IGF1R可能是这种恶性肿瘤预后不良的潜在标志物。

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