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High Mobility Group Box 1 (HMGB1) Predicts Invasion and Poor Prognosis of Glioblastoma Multiforme via Activating AKT Signaling in an Autocrine Pathway

Peng Cheng, Yun Ma, Zhiqiang Gao, Lingling Duan

(Department of Critical Care Medicine, Yidu Central Hospital of Weifang, Weifang, Shandong, China (mainland))

Med Sci Monit 2018; 24:8916-8924

DOI: 10.12659/MSM.912104

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 AND 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 GBM.

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