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Increased expression of Capn4 is associated with the malignancy of human glioma.

ABSTRACT: AIMS:Recent evidence indicates that the increased expression of calpain small subunit 1 (Capn4) is associated with tumorigenesis. This study was designed to explore the role which Capn4 plays in human glioma. METHODS:We detected the expression of Capn4 by immunohistochemistry in tissue microarrays and tissue samples. Following the down-regulation of Capn4 in glioma cell lines by a specific short hairpin RNA, the function of Capn4 in invasion, migration, and proliferation was assessed. We then evaluated the prognostic role of Capn4 using univariate and multivariate analysis in 94 glioblastoma (GBM) patients. RESULTS:Glioma tissues exhibited notably higher expression of Capn4 compared with control brain tissues and was positively correlated with histological malignancy. The down-regulation of Capn4 in glioma cells led to a decrease in invasion and migration in vitro. Through univariate analysis, the prognosis of GBM patients with Capn4 overexpression was significantly poorer with respect to progression-free survival (PFS) and overall survival (OS). Based on the results of the multivariate analysis, Capn4(high) was demonstrated to be a negative independent prognostic indicator for PFS and OS in GBM patients. CONCLUSION:The overexpression of Capn4 is a novel negative prognostic marker, and Capn4 may be used as a new target in therapeutic strategies for human glioma.

SUBMITTER: Cai JJ

PROVIDER: S-EPMC6492991 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Increased expression of Capn4 is associated with the malignancy of human glioma.

Cai Jia-Jun JJ Qi Zeng-Xin ZX Hua Wei W Zhu Jing-Jing JJ Zhang Xin X Yao Yu Y Mao Ying Y

CNS neuroscience & therapeutics 20140315 6

<h4>Aims</h4>Recent evidence indicates that the increased expression of calpain small subunit 1 (Capn4) is associated with tumorigenesis. This study was designed to explore the role which Capn4 plays in human glioma.<h4>Methods</h4>We detected the expression of Capn4 by immunohistochemistry in tissue microarrays and tissue samples. Following the down-regulation of Capn4 in glioma cell lines by a specific short hairpin RNA, the function of Capn4 in invasion, migration, and proliferation was asses ...[more]

PMID: 24628706

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Project description:BackgroundAmbiguity in malignant transformation of glioma has made prognostic diagnosis very challenging. Tumor malignant transformation is closely correlated with specific alterations of the metabolic profile. Exploration of the underlying metabolic alterations in glioma cells of different malignant degree is therefore vital to develop metabolic biomarkers for prognosis monitoring.MethodsWe conducted (1)H nuclear magnetic resonance (NMR)-based metabolic analysis on cell lines (CHG5, SHG44, U87, U118, U251) developed from gliomas of different malignant grades (WHO II and WHO IV). Several methods were applied to analyze the (1)H-NMR spectral data of polar extracts of cell lines and to identify characteristic metabolites, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), fuzzy c-means clustering (FCM) analysis and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). The expression analyses of glial fibrillary acidic protein (GFAP) and matrix metal proteinases (MMP-9) were used to assess malignant behaviors of cell lines. GeneGo pathway analysis was used to associate characteristic metabolites with malignant behavior protein markers GFAP and MMP-9.ResultsStable and distinct metabolic profiles of the five cell lines were obtained. The metabolic profiles of the low malignancy grade group (CHG5, SHG44) were clearly distinguished from those of the high malignancy grade group (U87, U118, U251). Seventeen characteristic metabolites were identified that could distinguish the metabolic profiles of the two groups, nine of which were mapped to processes related to GFAP and MMP-9. Furthermore, the results from both quantitative comparison and metabolic correlation analysis indicated that the significantly altered metabolites were primarily involved in perturbation of metabolic pathways of tricarboxylic acid (TCA) cycle anaplerotic flux, amino acid metabolism, anti-oxidant mechanism and choline metabolism, which could be correlated with the changes in the glioma cells' malignant behaviors.ConclusionsOur results reveal the metabolic heterogeneity of glioma cell lines with different degrees of malignancy. The obtained metabolic profiles and characteristic metabolites are closely associated with the malignant features of glioma cells, which may lay the basis for both determining the molecular mechanisms underlying glioma malignant transformation and exploiting non-invasive biomarkers for prognosis monitoring.

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Increased expression of Capn4 is associated with the malignancy of human glioma.

Publications

Increased expression of Capn4 is associated with the malignancy of human glioma.

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