title: Prognostic significance of kappaB-Ras1 expression in gliomas.
abstract: Nuclear factor (NF)-kappa-B is a pleiotropic transcriptional regulator that plays important roles in cell differentiation, growth, tumorigenesis, and apoptosis. Constitutive NF-kappa-B is overexpressed and activated in various tumors, including gliomas. Here, we investigated the expression of NF-kappa-B inhibitor interacting ras-like protein 1 (κB-Ras1), which is one of the most important negative modulators of NF-kappa-B, and a well-known proliferation biomarker survivin protein. We performed immunohistochemistry and western blot analysis on 154 glioma specimens and 3 non-neoplastic brain parenchyma specimens. Immunohistochemistry showed a strong-to-weak range of κB-Ras1 staining with increasing pathologic grade of glioma (P = 0.000). Immunoreactivity scores of κB-Ras1 were 8.15 ± 0.72 in non-neoplastic brain parenchyma, 5.00 ± 0.29 in low-grade gliomas, 3.89 ± 0.30 in anaplasia astrocytomas, and 2.78 ± 0.25 in glioblastomas. In contrast, the immunoreactivity of survivin increased with pathological grade in gliomas. The immunohistochemical data were in line with the results from western blot analysis. Moreover, a non-parametric analysis revealed that the attenuated κB-Ras1 expression was correlated with elevated survivin expression, large tumor diameter, frequent intra-tumor necrosis, and worse overall survival. These results indicated that κB-Ras1 was down-regulated in gliomas compared to non-neoplastic brain parenchyma, and the expression was even lower in glioblastomas. In addition, multivariate analysis showed that κB-Ras1 expression and intra-tumor necrosis were two important prognostic factors identified by the Cox proportional hazards model. Taken together, our study suggests that glioma patients with lower κB-Ras1 expression have a worse prognosis, which is partly due to NF-kappa-B pathway-mediated aberrant proliferation of tumor cells.
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, No.17 Changle Western Road, 710032 Xi'an, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.forename: Yangang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Bolin
authors.initials: B
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D018631:ras Proteins