Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Rd, Shanghai, 200003, China.
J Neurooncol. 2012 Nov;110(2):195-203. doi: 10.1007/s11060-012-0970-9. Epub 2012 Sep 13.
Golgi phosphoprotein-3 (GOLPH3), an important protein in mammalian target of rapamycin (mTOR) signaling, is overexpressed in and correlates with the pathological grade of glioma. However, the potential correlation between GOLPH3 and clinical outcome in patients with glioblastoma multiforme (GBM) remains unknown. In this study, we examined GOLPH3 expression in GBM by tissue microarray and correlated this measure to patient outcome. GOLPH3 expression in tumor tissue from 97 primary GBM patients was examined by tissue microarray and immunohistochemistry. Potential effects of GOLPH3 on tumor growth were also examined in representative cell lines (U251 and U87) by downregulating GOLPH3 with RNA interference. For this cohort, the median overall survival (OS) was 12 months [95 % confidence interval (CI): 10.31-13.69 months], and the median progression-free survival (PFS) was 10 months (95 % CI: 7.33-12.67 months). Tissue microarray analysis revealed high GOLPH3 expression in 40 patients (40/97, 41.2 %) and low GOLPH3 expression in the remaining 57 patients (57/97, 58.8 %). Log-rank test showed that patients with low GOLPH3 expression had significantly longer median OS (15 versus 10 months in patients with high GOLPH3 expression, p = 0.009) and median PFS (12 versus 7 months, p = 0.015). Univariate and Cox analysis indicated that GOLPH3 was an independent prognostic factor for OS and PFS. In in vitro experiments, GOLPH3 downregulation by small interfering RNA (siRNA) suppressed proliferation and clonogenic growth in cultured cell lines. These findings demonstrate that high GOLPH3 expression is associated with poor outcome of GBM patients.
高尔基磷蛋白 3（GOLPH3）是哺乳动物雷帕霉素靶蛋白（mTOR）信号通路中的一种重要蛋白，在神经胶质瘤中过度表达，并与病理分级相关。然而，GOLPH3 与多形性胶质母细胞瘤（GBM）患者临床结局之间的潜在相关性尚不清楚。在本研究中，我们通过组织微阵列检测了 GBM 中的 GOLPH3 表达，并将其与患者的预后进行了相关性分析。使用组织微阵列和免疫组织化学检测了 97 例原发性 GBM 患者肿瘤组织中的 GOLPH3 表达。通过 RNA 干扰下调 GOLPH3 在代表性细胞系（U251 和 U87）中的表达，还研究了 GOLPH3 对肿瘤生长的潜在影响。对于该队列，中位总生存期（OS）为 12 个月[95%置信区间（CI）：10.31-13.69 个月]，中位无进展生存期（PFS）为 10 个月（95%CI：7.33-12.67 个月）。组织微阵列分析显示，40 例患者（40/97，41.2%）中 GOLPH3 高表达，57 例患者（57/97，58.8%）中 GOLPH3 低表达。对数秩检验显示，GOLPH3 低表达的患者中位 OS 明显更长（高 GOLPH3 表达患者为 15 个月比 10 个月，p=0.009），中位 PFS 也更长（12 个月比 7 个月，p=0.015）。单因素和 Cox 分析表明，GOLPH3 是 OS 和 PFS 的独立预后因素。在体外实验中，小干扰 RNA（siRNA）下调 GOLPH3 抑制了培养细胞系的增殖和克隆形成生长。这些发现表明，GOLPH3 高表达与 GBM 患者的不良预后相关。
