Expression of GRK2 and IGF1R in hepatocellular carcinoma: clinicopathological and prognostic significance
Expression of GRK2 and IGF1R in hepatocellular carcinoma: clinicopathological and prognostic significance
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GRK2 和 IGF1R 在肝细胞癌中的表达：临床病理学和预后意义
DOI：
10.1136/jclinpath-2016-203998
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发表时间：
2017-09-01
影响因子：
3.4
通讯作者：
Jin, Ye
中科院分区：
文献类型：
--
作者：
Lin, Song-Bai;Zhou, Li;Jin, Ye
目的 研究表明，G 蛋白偶联受体激酶 2 (GRK2) 负向调节肝细胞癌 (HCC) 中的胰岛素样生长因子 1 受体 (IGF1R) 信号通路。本研究的目的是评估 GRK2 和 IGF1R 在 HCC 中的临床病理学和预后意义。方法首先采用基于组织芯片的免疫组织化学方法检测156例HCC患者中GRK2和IGF1R的表达。然后将染色结果（称为 H 评分）与临床病理学变量和患者生存率相关联。最后，GRK2 和 IGF1R 的预后价值在公开的 TCGA（癌症基因组图谱）RNA 测序数据库中得到了验证。结果 GRK2 染色的 H 值（肿瘤组织中显着低于非肿瘤组织）与 IGF1R 染色的 H 值呈负相关，且趋势相反。除了肿瘤 IGF1R 表达与肿瘤-淋巴结-转移阶段之间的关系外，没有发现这些蛋白质的临床病理学意义。在单变量分析中，IGF1R 高表达预示总体生存率和无病生存率较差，而 GRK2 则不能预测预后。在多变量分析中，IGF1R 对于总生存期具有重要意义。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。
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.