Association between glioblastoma cell-derived vessels and poor prognosis of the patients

Cancer Communications

article

Xin Mei¹  Jing Wang¹  Zhong-Ping Chen¹  Yin-Sheng Chen¹  Qing-Ping Zhang³  Fu-Rong Chen¹  Shao-Yan Xi¹  Ya-Kang Long⁴  Ji Zhang¹  Hai-Ping Cai¹  Chao Ke¹ 

[1] Department of Neurosurgery/Neuro-oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center;Department of Neurosurgery, Sun Yat-sen Memorial Hospital;Department of Neurosurgery, Huazhong University of Science and Technology Union Shenzhen Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center (Shenzhen Nanshan People's Hospital）;Department of Molecular Diagnostics, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center

关键词: endothelial differentiation;    endothelium-dependent vessel;    extracellular matrix-dependent vessel;    glioblastoma cell-derived vessel;    Glioblastoma;    MGMT promoter methylation;    microcirculation;    mosaic vessel;    prognosis;    vasculogenic mimicry;   

DOI  :  10.1002/cac2.12026

学科分类：社会科学、人文和艺术（综合）

来源: Springer

【 摘 要 】

Background Vessels with different microcirculation patterns are required for glioblastoma (GBM) growth. However, details of the microcirculation patterns in GBM remain unclear. Here, we examined the microcirculation patterns of GBM and analyzed their roles in patient prognosis together with two well-known GMB prognosis factors (O 6 -methylguanine DNA methyltransferase [MGMT] promoter methylation status and isocitrate dehydrogenase [IDH] mutations). Methods Eighty GBM clinical specimens were collected from patients diagnosed between January 2000 and December 2012. The microcirculation patterns, including endothelium-dependent vessels (EDVs), extracellular matrix-dependent vessels (ECMDVs), GBM cell-derived vessels (GDVs), and mosaic vessels (MVs), were evaluated by immunohistochemistry (IHC) and immunofluorescence (IF) staining in both GBM clinical specimens and xenograft tissues. Vascular density assessments and three-dimensional reconstruction were performed. MGMT promoter methylation status was determined by methylation-specific PCR, and IDH1/2 mutations were detected by Sanger sequencing. The relationship between the microcirculation patterns and patient prognosis was analyzed by Kaplan-Meier method. Results All 4 microcirculation patterns were observed in both GBM clinical specimens and xenograft tissues. EDVs were detected in all tissue samples, while the other three patterns were observed in a small number of tissue samples (ECMDVs in 27.5%, GDVs in 43.8%, and MVs in 52.5% tissue samples). GDV-positive patients had a median survival of 9.56 months versus 13.60 months for GDV-negative patients ( P  = 0.015). In MGMT promoter-methylated cohort, GDV-positive patients had a median survival of 6.76 months versus 14.23 months for GDV-negative patients ( P  = 0.022). Conclusion GDVs might be a negative predictor for the survival of GBM patients, even in those with MGMT promoter methylation.

【 授权许可】

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