title: High Jagged1 expression is associated with poor outcome in primary glioblastoma.
abstract: Glioblastoma is a highly aggressive brain tumor. Aberrant Notch pathway has been implicated in the formation and progression of glioblastoma. The present study attempted to investigate the expression of Notch ligand Jagged1 and its association with patient outcome in primary glioblastoma. Tumor tissues from 82 patients with primary glioblastoma were analyzed using immunohistochemistry for Jagged1 expression. Relationships between Jagged1 expression and clinical features (age, gender, KPS, symptom duration, extent of resection and Ki67 index) were evaluated. The prognostic value of Jagged1 was assessed using the Kaplan-Meier survival estimates and the Cox proportional hazard models. Immunohistochemistry results showed markedly increased Jagged1 expression in glioblastoma tissues compared to adjacent non-neoplastic brain tissues. Univariate analysis documented that high Jagged1 expression in tumor cells (TC) and endothelial cells (EC) were both statistically associated with reduced time to progression (TTP) (P < 0.001 for TC, P = 0.001 for EC) and overall survival (OS) (P < 0.001 for TC, P = 0.003 for EC) in primary glioblastoma. The median TTP (P < 0.001) and OS (P = 0.001) were higher in patients with dual-low Jagged1 expression in TC and EC compared to those in patients with non-dual Jagged1 expression and dual high expression. By multivariate survival analysis, we found that high Jagged1 expression in both tumor cells and endothelial cells was independent unfavorable prognostic factors TTP (P < 0.001 for TC, P < 0.001 for TC) and OS (P < 0.001 for TC, P < 0.001 for TC) in primary glioblastoma patients. Jagged1-Notch signaling plays an important role in the progress of glioblastoma. Jagged1 expression may be used as an independent prognosis factor in patients with glioblastoma.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian, China.
authors.forename: Xian-Xin
authors.initials: XX
authors.lastname: Qiu
authors.forename: Chen-Hong
authors.initials: CH
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: You
authors.forename: Bi-Juan
authors.initials: BJ
authors.lastname: Chen
authors.forename: Xing-Fu
authors.initials: XF
authors.lastname: Wang
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Chen
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000096:biosynthesis*; D000072100:Jagged-1 Protein; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000072099:Serrate-Jagged Proteins; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins