High Mobility Group Box 1 (HMGB1) Predicts Invasion and Poor Prognosis of Glioblastoma Multiforme via Activating AKT Signaling in an Autocrine Pathway
High Mobility Group Box 1 (HMGB1) Predicts Invasion and Poor Prognosis of Glioblastoma Multiforme via Activating AKT Signaling in an Autocrine Pathway
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DOI：
10.12659/msm.912104
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发表时间：
2018-12-09
影响因子：
3.1
通讯作者：
Duan, Lingling
中科院分区：
文献类型：
--
作者：
Cheng, Peng;Ma, Yun;Duan, Lingling
背景资料：作为一种核蛋白和分泌蛋白，HMGB 1参与许多细胞过程，如增殖、转录和炎症。材料/方法：采用免疫组化方法检测116例多形性胶质母细胞瘤（GBM）组织中HMGB 1的表达，并采用qRT-PCR方法检测12对GBM组织及癌旁组织中HMGB 1的表达。采用卡方检验分析HMGB 1与临床病理因素的相关性。采用单因素分析和多因素分析评价HMGB 1对预后的影响。结果：在本研究中，HMGB 1高表达的患者占所有患者的42.2%，高表达的患者占所有患者的42.2%。高HMGB 1与低生存率相关，并被确定为GBM的独立预后因素。细胞内HMGB 1基因的敲低可显著降低GBM细胞的增殖和侵袭能力。结论：HMGB 1是GBM患者预后不良的独立预后标志物。GBM细胞释放的HMGB 1可以激活AKT和ERK信号通路，并通过这一自分泌通路促进GBM细胞的侵袭，表明抗HMGB 1治疗可能是一种有希望的治疗方法。
Background: As a nuclear protein and a secreted protein, HMGB1 is involved in many cellular processes such as proliferation, transcription, and inflammation. The overexpression of HMGB1 in various types of cancers is reported, but its clinical significance and prognostic value in glioblastoma multiforme (GBM) has not been well defined.Material/Methods: The expression of HMGB1 in 116 patients with GBM was investigated with immunohistochemistry, and was detected with qRT-PCR in 12 pairs of tumor tissues and adjacent tissues. The correlations between HMGB1 and clinicopathological factors were analyzed with the chi-square test. Prognostic value of HMGB1 was evaluated with univariate analysis and multivariate analysis. By knocking down HMGB1 by siRNA, the functions of HMGB1 in progression of GBM cell lines were investigated by experiments in vitro.Results: In our study, patients with high HMGB1 expression accounted for 42.2% of all the patients. High HMGB1 was correlated with low survival rates and was identified as an independent prognostic factor of GBM. Knockdown of intracellular HMGB1 remarkably decreased GBM cells proliferation and invasion. In hypoxia, intracellular HMGB1 of GBM cells was released out and activated AKT and ERK signaling pathways, thus promoting GBM cell invasion in this autocrine pathway.Conclusions: HMGB1 is an independent prognostic biomarker for unfavorable prognosis of patients with GBM. Released HMGB1 of GBM cells can activate AKT and ERK signaling pathways and promote GBM cells invasion in this autocrine pathway, indicating that anti-HMGB1 therapy may be a promising treatment for