Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Minimally Invasive Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, 100142 Beijing, China.
J Transl Med. 2014 Jan 21;12:15. doi: 10.1186/1479-5876-12-15.
Golgi phosphoprotein 3 (GOLPH3) has been validated as a potent oncogene involved in the progression of many types of solid tumors, and its overexpression is associated with poor clinical outcome in many cancers. However, it is still unknown the association of GOLPH3 expression with the prognosis of colorectal cancer (CRC) patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy.
The expression of GOLPH3 was determined by qRT-PCR and immunohistochemistry in colorectal tissues from CRC patients treated with 5-FU based adjuvant chemotherapy after surgery. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. The effects of GOLPH3 on 5-FU sensitivity were examined in CRC cell lines.
GOLPH3 expression was elevated in CRC tissues compared with matched adjacent noncancerous tissues. Kaplan-Meier survival curves indicated that high GOLPH3 expression was significantly associated with prolonged disease-free survival (DFS, P = 0.002) and overall survival (OS, P = 0.011) in patients who received 5-FU-based adjuvant chemotherapy. Moreover, multivariate analysis showed that GOLPH3 expression was an independent prognostic factor for DFS in CRC patients treated with 5-FU-based chemotherapy (HR, 0.468; 95%CI, 0.222-0.987; P = 0.046). In vitro, overexpression of GOLPH3 facilitated the 5-FU chemosensitivity in CRC cells; while siRNA-mediated knockdown of GOLPH3 reduced the sensitivity of CRC cells to 5-FU-induced apoptosis.
Our results suggest that GOLPH3 is associated with prognosis in CRC patients treated with postoperative 5-FU-based adjuvant chemotherapy, and may serve as a potential indicator to predict 5-FU chemosensitivity.
高尔基磷酸蛋白 3（GOLPH3）已被验证为一种强效致癌基因，参与多种实体瘤的进展，其过表达与许多癌症的不良临床结局相关。然而，GOLPH3 表达与接受基于 5-氟尿嘧啶（5-FU）的辅助化疗的结直肠癌（CRC）患者预后的关系尚不清楚。
通过 qRT-PCR 和免疫组织化学法检测接受基于 5-FU 的辅助化疗后手术的 CRC 患者的结直肠组织中 GOLPH3 的表达。分析 GOLPH3 与临床病理特征和预后的关系。在 CRC 细胞系中研究 GOLPH3 对 5-FU 敏感性的影响。
与匹配的相邻非癌组织相比，CRC 组织中 GOLPH3 的表达升高。Kaplan-Meier 生存曲线表明，高 GOLPH3 表达与接受基于 5-FU 的辅助化疗的患者无病生存期（DFS，P=0.002）和总生存期（OS，P=0.011）延长显著相关。此外，多变量分析显示，GOLPH3 表达是接受基于 5-FU 化疗的 CRC 患者 DFS 的独立预后因素（HR，0.468；95%CI，0.222-0.987；P=0.046）。体外实验中，GOLPH3 的过表达促进了 CRC 细胞对 5-FU 的化疗敏感性；而 siRNA 介导的 GOLPH3 敲低降低了 CRC 细胞对 5-FU 诱导的细胞凋亡的敏感性。
我们的研究结果表明，GOLPH3 与接受术后基于 5-FU 的辅助化疗的 CRC 患者的预后相关，并且可能作为预测 5-FU 化疗敏感性的潜在指标。
