Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis
Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis
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DOI：
10.1007/s11060-012-0970-9
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发表时间：
2012-11-01
影响因子：
3.9
通讯作者：
Chen, Juxiang
中科院分区：
文献类型：
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作者：
Zhou, Jinxu;Xu, Tao;Chen, Juxiang
高尔基磷蛋白-3(GOLPH3)是哺乳动物雷帕霉素(MTOR)信号转导通路中的重要蛋白，在脑胶质瘤中呈高表达，并与肿瘤的病理分级有关。然而，GOLPH3与多形性胶质母细胞瘤(GBM)患者临床预后的潜在相关性仍不清楚。在这项研究中，我们用组织芯片检测了GOLPH3在基底膜中的表达，并将这一指标与患者的预后相关联。应用组织芯片和免疫组织化学方法检测97例原发性GBM患者肿瘤组织中GOLPH3的表达。通过RNA干扰下调GOLPH3的表达，研究了GOLPH3对肿瘤生长的潜在影响。中位总生存期(OS)为12个月[95%可信区间(CI)：10.31-13.69个月]，中位无进展生存期(PFS)为10个月(95%可信区间：7.33-12.67个月)。组织芯片检测GOLPH3高表达40例(40/97，41.2%)，低表达57例(57/97，58.8%)。LOG-RANK检验显示，GOLPH3低表达患者的中位OS(15个月对10个月，p=0.009)和中位PFS(12个月对7个月，p=0.015)显著延长。单因素分析和Cox回归分析显示，GOLPH3是OS和PFS的独立预后因素。在体外实验中，GOLPH3被小干扰RNA(SiRNA)下调，抑制了培养的细胞系的增殖和克隆生长。这些结果表明，GOLPH3的高表达与GBM患者的预后不良有关。
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 down-regulation 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.