Primary glioblastoma multiforme tumors and recurrence Comparative analysis of the danger signals HMGB1, HSP70, and calreticulin
Primary glioblastoma multiforme tumors and recurrence Comparative analysis of the danger signals HMGB1, HSP70, and calreticulin
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DOI：
10.1007/s00066-015-0926-z
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发表时间：
2016-03-01
影响因子：
3.1
通讯作者：
Gaipl, Udo S.
中科院分区：
文献类型：
--
作者：
Muth, Carolin;Ruebner, Yvonne;Gaipl, Udo S.
目的 多形性胶质母细胞瘤（GBM）是最常见且侵袭性最强的脑肿瘤。尽管多模式疗法有所改进，但在大多数病例中肿瘤仍会复发。患者生存率的差异表明肿瘤具有很大的异质性以及对治疗的不同反应。高迁移率族蛋白B1（HMGB1）、热休克蛋白70（HSP70）和钙网蛋白（CRT）等危险信号由于与肿瘤进展以及抗肿瘤免疫反应的诱导相关，是生物标志物的候选者。这些危险信号在多种肿瘤类型中都有过度表达的报道；然而，它们在GBM中的作用仍不明确。对于大多数肿瘤实体，仍缺乏对其在原发肿瘤与相应复发肿瘤中表达的直接比较。
患者和方法 因此，我们通过免疫组织化学对9例初发GBM患者的原发肿瘤及其相应复发肿瘤中的危险信号HMGB1、HSP70和CRT进行了表达分析。
结果 HMGB1在原发肿瘤中高表达，在相应复发肿瘤中显著降低。与原发肿瘤相比，复发肿瘤中细胞外HSP70的表达显著增加。CRT在原发肿瘤中普遍高表达，在复发肿瘤中略有增加。
结论 复发肿瘤中HMGB1表达降低、细胞外HSP70表达增加以及CRT表达增加的组合似乎对患者生存有益。HMGB1、细胞外HSP70和CRT可作为GBM患者预后的潜在生物标志物综合考虑。
Purpose Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor. Despite improved multimodal therapies, the tumor recurs in most cases. Diverging patient survival suggests great tumor heterogeneity and different therapy responses. Danger signals such as high-mobility group box protein 1 (HMGB1), heat shock protein 70 (HSP70), and calreticulin (CRT) are biomarker candidates, due to their association with tumor progression versus induction of antitumor immune responses. Overexpression of these danger signals has been reported for various types of tumors; however, their role in GBM is still elusive. A direct comparison of their expression in the primary tumor versus the corresponding relapse is still lacking for most tumor entities.Patients and methods We therefore performed an expression analysis by immunohistochemistry of the danger signals HMGB1, HSP70, and CRT in primary tumors and the corresponding relapses of 9 patients with de novo GBM.Results HMGB1 was highly expressed in primary tumors with a significant reduction in the respective relapse. The extracellular HSP70 expression was significantly increased in the relapse compared to the primary tumor. CRT was generally highly expressed in the primary tumor, with a slight increase in the relapse.Conclusion The combination of a decreased expression of HMGB1, an increased expression of extracellular HSP70, and an increased expression of CRT in the relapse seems to be beneficial for patient survival. HMGB1, extracellular HSP70, and CRT could be taken into concerted consideration as potential biomarkers for the prognosis of patients with GBM.