Oblinger J L, Pearl D K, Boardman C L, Saqr H, Prior T W, Scheithauer B W, Jenkins R B, Burger P C, Yates A J
Department of Pathology, The Ohio State University, Columbia, OH, USA.
Neuropathol Appl Neurobiol. 2006 Aug;32(4):410-8. doi: 10.1111/j.1365-2990.2006.00742.x.
Glioblastoma multiforme (GBM) is the most common and aggressive primary human brain tumour in adults with an average survival of 11 months. The 2-year survival is less than 10%, and only a small proportion of patients are alive at 3 years. Despite improved treatment strategies and aggressive therapy, the prognosis of GBM has changed little in past decades. Thus, any test that can reliably and rapidly diagnose the tumour and predict patient survival could be a valuable tool. Herein we report the use of quantitative real-time polymerase chain reaction (PCR) to quantify five glycosyltransferase transcripts in gliomas. Our results indicate that measuring GM1 synthase (beta-1,3 galactosyltransferase) mRNA may provide a useful method for segregating GBMs from other types of gliomas. In these studies, 97% of gliomas (36/37 tumours) below a threshold value had a diagnosis of GBM compared with 49% (52/106 tumours) above the threshold. More importantly, the increased expression of GD3 synthase mRNA in combination with decreased GalNAcT message correlated with increased survival in 79 GBM patients (proportional hazards model controlling for age, P = 0.02). These data were further corroborated by a data analysis from one of our previous studies on gangliosides of 80 GBMs, in which increased amounts of GM3 and GD3 (which accumulate in the absence of GalNAcT) correlated with a longer survival (P < 0.01). Thus, measuring GalNAcT and GD3 transcripts may provide a rapid method to assess prognosis in GBM patients. In summary, the data indicate that measuring glycosyltransferase mRNA levels by real-time PCR may be clinically useful for determining both diagnosis and prognosis in GBM patients.
多形性胶质母细胞瘤(GBM)是成人中最常见且侵袭性最强的原发性脑肿瘤,平均生存期为11个月。其2年生存率低于10%,3年时仅有一小部分患者存活。尽管治疗策略有所改进且采取了积极的治疗方法,但在过去几十年中GBM的预后几乎没有变化。因此,任何能够可靠且快速诊断肿瘤并预测患者生存情况的检测方法都可能是一种有价值的工具。在此我们报告了使用定量实时聚合酶链反应(PCR)来定量胶质瘤中的五种糖基转移酶转录本。我们的结果表明,测量GM1合酶(β-1,3半乳糖基转移酶)mRNA可能为区分GBM与其他类型的胶质瘤提供一种有用的方法。在这些研究中,低于阈值的胶质瘤中有97%(36/37个肿瘤)被诊断为GBM,而高于阈值的为49%(52/106个肿瘤)。更重要的是,在79例GBM患者中,GD3合酶mRNA表达增加与GalNAcT信息减少相结合与生存期延长相关(控制年龄的比例风险模型,P = 0.02)。我们之前一项关于80例GBM神经节苷脂的研究中的数据分析进一步证实了这些数据,其中GM3和GD3(在没有GalNAcT的情况下积累)含量增加与生存期延长相关(P < 0.01)。因此,测量GalNAcT和GD3转录本可能为评估GBM患者的预后提供一种快速方法。总之,数据表明通过实时PCR测量糖基转移酶mRNA水平在临床上可能有助于确定GBM患者的诊断和预后。