Czapski Bartosz, Baluszek Szymon, Herold-Mende Christel, Kaminska Bozena
Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland.
Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
Contemp Oncol (Pozn). 2018 Mar;22(1A):81-85. doi: 10.5114/wo.2018.73893. Epub 2018 Mar 5.
Glioblastoma (GBM) is the most common and most aggressive type of primary brain tumour in adults. It represents 54% of all gliomas and 16% of all brain tumours (Ostrom et al. 2016). Despite surgery and treatment with radiotherapy plus an oral alkylating agent, temozolomide (TMZ), tumours invariably recur, and the patient survival is an average of ~14-16 months. In this review we summarise the current understanding of multiple factors that may affect survival of patients with GBMs. In particular, we discuss recent advancements in surgery and detection of genomic-based markers with prognostic values, such as mutations, gene promoter methylation, and gene promoter alterations. We address the issue of tumour heterogeneity and evolution that may result in different parts of the same tumour exhibiting different GBM subtypes and in subtype switching, which may restrict the usefulness of the expression-based classification as a prognostic marker before relapse. The determinants of long-term survival in patients with wt GBM, beyond promoter methylation, remain to be identified, and even the absence of both mutations and promoter methylation does not preclude long-term survival. These findings suggest that host-derived factors, such as immune system responsiveness may contribute to long-term survival in such patients. We report the results of high-throughput approaches, suggesting links between long-term survival and enhanced immune-related gene expression. The further search for new gene candidates, promoter methylation status, and specific features of host immunity should provide prognostic biomarkers for the evaluation of survival of IDH1 wild-type/non-G-CIMP GBMs.
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类型。它占所有胶质瘤的54%，占所有脑肿瘤的16%（奥斯特罗姆等人，2016年）。尽管进行了手术以及放疗加口服烷化剂替莫唑胺（TMZ）治疗，但肿瘤总是会复发，患者的平均生存期约为14 - 16个月。在本综述中，我们总结了目前对可能影响GBM患者生存的多种因素的理解。特别是，我们讨论了手术以及具有预后价值的基于基因组的标志物检测方面的最新进展，如突变、基因启动子甲基化和基因启动子改变。我们探讨了肿瘤异质性和进化问题，这可能导致同一肿瘤的不同部位表现出不同的GBM亚型以及亚型转换，这可能会限制基于表达的分类作为复发前预后标志物的实用性。野生型GBM患者长期生存的决定因素，除了启动子甲基化之外，仍有待确定，而且即使没有突变和启动子甲基化也不能排除长期生存的可能性。这些发现表明，宿主来源的因素，如免疫系统反应性，可能有助于此类患者的长期生存。我们报告了高通量方法的结果，表明长期生存与免疫相关基因表达增强之间存在联系。进一步寻找新的基因候选物、启动子甲基化状态以及宿主免疫的特定特征，应该能够为评估异柠檬酸脱氢酶1野生型/非CpG岛甲基化表型GBM患者的生存情况提供预后生物标志物。
