Mechanistic insight into glioma through spatially multidimensional proteomics.

Characterizing the tumor microenvironment at the molecular level is essential for understanding the mechanisms of tumorigenesis and evolution. However, the specificity of the blood proteome in localized region of the tumor and its linkages with other systems is difficult to investigate. Here, we propose a spatially multidimensional comparative proteomics strategy using glioma as an example. The blood proteome signature of tumor microenvironment was specifically identified by in situ collection of arterial and venous blood from the glioma region of the brain for comparison with peripheral blood. Also, by integrating with different dimensions of tissue and peripheral blood proteomics, the information on the genesis, migration, and exchange of glioma-associated proteins was revealed, which provided a powerful method for tumor mechanism research and biomarker discovery. The study recruited multidimensional clinical cohorts, allowing the proteomic results to corroborate each other, reliably revealing biological processes specific to gliomas, and identifying highly accurate biomarkers.

Assessment of plasma soluble Tie-2 level to distinguish moyamoya disease from atherosclerotic cerebrovascular disease and predict postoperative neovascularization.

OBJECTIVE: Moyamoya disease (MMD) is a chronic steno-occlusive cerebrovascular disease and features the formation of hazy collateral vessels at the base of the brain. Angiopoietin (Ang)-1 and -2, their receptor Tie-2, and vascular endothelial growth factor (VEGF) that regulate angiogenesis might be important in MMD pathophysiology and postoperative collateral formation. The goal of this study was to determine whether levels of these angiogenic factors could predict collateralization in patients with MMD. METHODS: A total of 196 patients with MMD and 57 with atherosclerotic cerebrovascular disease serving as controls were enrolled. Ang-1, Ang-2, Tie-2, and VEGF mRNA levels were analyzed in middle cerebral artery (MCA) arterial wall specimens by using real-time quantitative polymerase chain reaction. MCA and peripheral plasma concentrations of Ang-1, Ang-2, soluble Tie-2 (sTie-2), and VEGF were examined by enzyme-linked immunosorbent assay. Cerebral arteriography was performed 6 months after bypass surgery to assess the postoperative collateralization. RESULTS: In MCA specimens, patients with MMD exhibited higher expression levels of Ang-1 and Ang-2 but lowered VEGF expression. The patients with MMD had significantly higher concentrations of Ang-1 and Ang-2 but lower levels of VEGF in MCA plasma. Peripheral plasma concentrations of these growth factors were not changed. MCA and peripheral plasma sTie-2 levels were both reduced in patients with MMD. The 6-month follow-up showed that patients with good collateral formation had lower sTie-2 levels in both MCA and peripheral plasma. Furthermore, the Suzuki stage and peripheral plasma sTie-2 level were significantly correlated with good postoperative collateral formation on multivariate analysis. CONCLUSIONS: Ang-1, Ang-2, Tie-2, and VEGF are involved in MMD pathogenesis. The peripheral plasma level of sTie-2 can differentiate MMD from atherosclerotic cerebrovascular disease and serve as a novel biomarker to predict postoperative collateral formation.

The Optimum Operative Time of Revascularization for Patients with Moyamoya Disease Following Acute Onset.

OBJECTIVE: Whether surgery should be performed in patients with acute onset of moyamoya disease (MMD) is controversial. This study aimed to determine optimum operative time for patients with MMD. METHODS: We retrospectively analyzed 57 patients with MMD admitted between January 2016 and June 2017. All patients consented to combined revascularization. Considering the time interval between acute onset of MMD and surgery, we divided all patients into an early group and later group (>90 days between MMD onset and surgery). We compared postoperative complications, neurologic improvement, and favorable outcome between groups to estimate optimum operative time of revascularization. RESULTS: More patients in the early group presented with ischemic events compared with the later group (18/28 vs. 11/29, P = 0.047). The difference in worst preoperative mRS score (≥3) between groups was not statistically significant (3/28 vs. 3/29, P = 0.964). Rate of postoperative complications in the early group was significantly higher than in the later group (39.2% vs. 13.7%, P = 0.029). There was neurologic improvement in 50.0% of patients in the early group and 75.9% of patients in the later group (P = 0.043). The rate of favorable outcome after revascularization in the later group (89.7%) was higher than in the early group (78.6%), but there was no significant difference (P = 0.251). CONCLUSIONS: It seems more reasonable to opt for delayed revascularization for patients with acute-onset MMD, but the decision must take into account the morbidity of ongoing ischemic or hemorrhagic events.