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Malignancy-associated metabolic profiling of human glioma cell lines using 1H NMR spectroscopy

作者:Wei Shao, Jinping Gu, Caihua Huang, Dan Liu, Huiying Huang, Zicheng Huang, Zhen Lin, Wensheng Yang, Kun Liu, Donghai Lin, Tianhai Ji · 发表于:Molecular Cancer · 年份:2014 · DOI:10.1186/1476-4598-13-197 · 被引用次数:61 · 研究领域:Metabolomics and Mass Spectrometry Studies、Advanced MRI Techniques and Applications、Cancer, Hypoxia, and Metabolism

BACKGROUND: Ambiguity 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. METHODS: We 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. RESULTS: Stable 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). Seven...