GOLPH3 is a novel marker of poor prognosis and a potential therapeutic target in human renal cell carcinoma.
GOLPH3 is a novel marker of poor prognosis and a potential therapeutic target in human renal cell carcinoma.
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DOI：
10.1038/bjc.2014.124
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发表时间：
2014-04-29
影响因子：
8.8
通讯作者：
Huang, R.
中科院分区：
文献类型：
--
作者：
Xue, Y.;Wu, G.;Liao, Y.;Xiao, G.;Ma, X.;Zou, X.;Zhang, G.;Xiao, R.;Wang, X.;Liu, Q.;Long, D.;Yang, J.;Xu, H.;Liu, F.;Liu, M.;Xie, K.;Huang, R.
据报道，高尔基体磷蛋白 3 (GOLPH3) 参与了多种人类癌症的发生。本研究旨在探讨GOLPH3在肾细胞癌（RCC）中的表达及其预后意义。同时，在细胞培养模型中进一步研究了GOLPH3在人RCC中的功能。通过实时定量 PCR 和蛋白质印迹法检测了 43 个新鲜肾细胞癌组织和配对的邻近正常肾组织中 GOLPH3 的表达。对另外 218 个 RCC 组织进行了 GOLPH3 的免疫组织化学分析。分析GOLPH3表达的临床意义。使用小干扰RNA（siRNA）在高丰度GOLPH3的Caki-1和786-O细胞中下调GOLPH3，并评估GOLPH3沉默对细胞增殖、迁移、体外侵袭和体内肿瘤生长的影响。大多数 RCC 临床组织标本中 GOLPH3 的表达在 mRNA 和蛋白质水平上均上调。临床病理分析显示，GOLPH3表达与T分期（P<0.001）、淋巴结状态（P=0.003）、远处转移（P<0.001）、肿瘤淋巴结转移（TNM）分期（P<0.001）和Fuhman分级（P=0.001）显着相关。 GOLPH3 的表达与 RCC 患者的总生存期和无复发生存期呈负相关。多变量分析表明GOLPH3表达是患者生存的独立预后指标。敲低 GOLPH3 表达可减少异种移植模型小鼠的细胞增殖、贴壁依赖性生长、迁移、侵袭和肿瘤生长。这些结果表明GOLPH3表达可能在RCC发生和进展中发挥重要作用，并且GOLPH3是RCC的预后生物标志物和有前途的治疗靶点。
Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. The present study was conducted to investigate the expression of GOLPH3 and its prognostic significance in renal cell carcinoma (RCC). Meanwhile, the function of GOLPH3 in human RCC was further investigated in cell culture models. Expression of GOLPH3 was examined in 43 fresh RCC tissues and paired adjacent normal renal tissues by real-time quantitative PCR and western blotting. Immunohistochemistry for GOLPH3 was performed on additional 218 RCC tissues. The clinical significance of GOLPH3 expression was analysed. Downregulation of GOLPH3 was performed using small-interfering RNA (siRNA) in Caki-1 and 786-O cells with high abundance of GOLPH3, and the effects of GOLPH3 silencing on cell proliferation, migration, invasion in vitro, and tumour growth in vivo were evaluated. Expression of GOLPH3 was upregulated in the majority of the RCC clinical tissue specimens at both mRNA and protein levels. Clinicopathological analysis showed that GOLPH3 expression was significantly correlated with T stage (P<0.001), lymph-node status (P=0.003), distant metastasis (P<0.001), tumour-node-metastasis (TNM) stage (P<0.001), and Fuhman grade (P=0.001). Expression of GOLPH3 was inversely correlated with both overall and recurrence-free survival of RCC patients. Multivariate analysis showed that GOLPH3 expression was an independent prognostic indicator for patient's survival. Knockdown of the GOLPH3 expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumour growth in xenograft model mice. These results suggest that GOLPH3 expression is likely to have important roles in RCC development and progression, and that GOLPH3 is a prognostic biomarker and a promising therapeutic target for RCC.
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