Jin Ye, Liang Zhi-Yong, Zhou Wei-Xun, Zhou Li
Clinical Research Laboratory, 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.
J Cancer. 2017 Jul 5;8(11):1972-1978. doi: 10.7150/jca.19201. eCollection 2017.
To investigate expression, clinical, pathologic and prognostic significances of G-protein-coupled receptor kinase 3 (GRK3) in hepatocellular carcinoma (HCC). Expression of GRK3 was detected using Western blotting and tissue microarray-based immunohistochemical staining in 8 and 395 patients (training set: n=164; validation set: n=231) with HCC underwent hepatectomy, respectively. GRK3 expression and its associations with cliniopathologic variables and tumor-specific survival were evaluated. Expression of GRK3 was lower in tumor than in non-tumor tissues from 4 out of 8 patients. In the training set, the H-score of tumoral GRK3 staining was much lower than that in adjacent non-tumor liver tissues. In addition, GRK3 was associated with tumor-node-metastasis (TNM) stage and serum α-fetoprotein (AFP) level. Patients with high GRK3 tumors were found to carry significantly better tumor-specific survival, compared with those with low GRK3 ones. Furthermore, GRK3 was identified as one of independent predictors of favorable prognosis, adjusted for clinicopathologic parameters. Importantly, these results were further validated in the independent validation set. In all patients and 7 out of 10 subgroups, GRK3 was also revealed to be prognostic. GRK3 is down-regulated and predicts good prognosis in HCC. Therefore, GRK3 might function as a tumor suppressor gene in HCC.
研究G蛋白偶联受体激酶3（GRK3）在肝细胞癌（HCC）中的表达、临床、病理及预后意义。分别采用蛋白质免疫印迹法和基于组织芯片的免疫组化染色检测了8例和395例接受肝切除术的HCC患者（训练集：n = 164；验证集：n = 231）中GRK3的表达。评估了GRK3的表达及其与临床病理变量和肿瘤特异性生存的关系。8例患者中有4例肿瘤组织中GRK3的表达低于非肿瘤组织。在训练集中，肿瘤组织GRK3染色的H评分远低于相邻的非肿瘤肝组织。此外，GRK3与肿瘤-淋巴结-转移（TNM）分期和血清甲胎蛋白（AFP）水平相关。与GRK3低表达的患者相比，GRK3高表达的患者具有显著更好的肿瘤特异性生存。此外，经临床病理参数校正后，GRK3被确定为良好预后的独立预测因子之一。重要的是，这些结果在独立验证集中得到了进一步验证。在所有患者及10个亚组中的7个亚组中，GRK3也显示出具有预后意义。GRK3在HCC中表达下调并预测良好预后。因此，GRK3可能在HCC中起肿瘤抑制基因的作用。
