Department of Urology, First Affiliated Hospital of Gannan Medical University, No. 23, Qing Nian Road, Ganzhou 341000, People's Republic of China.
Department of Graduate School, Medical College of Nanchang University, Nanchang, People's Republic of China.
Br J Cancer. 2014 Apr 29;110(9):2250-60. doi: 10.1038/bjc.2014.124. Epub 2014 Mar 4.
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.
高尔基磷酸蛋白 3（GOLPH3）已被报道参与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。
采用实时定量 PCR 和 Western blot 检测 43 例新鲜 RCC 组织及其配对的正常肾组织中 GOLPH3 的表达。对另外 218 例 RCC 组织进行 GOLPH3 的免疫组织化学检测。分析 GOLPH3 表达的临床意义。采用小干扰 RNA（siRNA）下调 Caki-1 和 786-O 细胞中高丰度的 GOLPH3，评估 GOLPH3 沉默对细胞增殖、迁移、侵袭的体外影响以及体内肿瘤生长的影响。
GOLPH3 在大多数 RCC 临床组织标本中的 mRNA 和蛋白水平均上调。临床病理分析显示，GOLPH3 的表达与 T 分期（P<0.001）、淋巴结状态（P=0.003）、远处转移（P<0.001）、TNM 分期（P<0.001）和 Fuhman 分级（P=0.001）显著相关。GOLPH3 的表达与 RCC 患者的总生存和无复发生存呈负相关。多因素分析显示，GOLPH3 的表达是患者生存的独立预后指标。下调 GOLPH3 的表达可降低细胞增殖、非依赖性生长、迁移、侵袭和异种移植模型小鼠的肿瘤生长。
这些结果表明，GOLPH3 的表达可能在 RCC 的发生和发展中具有重要作用，GOLPH3 是 RCC 的预后标志物和有前途的治疗靶点。
