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Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients.
Yong, William H; Shabihkhani, Maryam; Telesca, Donatello; Yang, Shuai; Tso, Jonathan L; Menjivar, Jimmy C; Wei, Bowen; Lucey, Gregory M; Mareninov, Sergey; Chen, Zugen; Liau, Linda M; Lai, Albert; Nelson, Stanley F; Cloughesy, Timothy F; Tso, Cho-Lea.
Afiliación
  • Yong WH; Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
  • Shabihkhani M; Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
  • Telesca D; Department of Biostatistics, University of California Los Angeles, Los Angeles, California, United States of America; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
  • Yang S; Department of Neurosurgery, General Hospital of Guangzhou Military Command, Guangzhou, China; Department of Surgery/Surgical-Oncology, University of California Los Angeles, Los Angeles, California, United States of America; Department of Neurosurgery, University of California Los Angeles, Los Angele
  • Tso JL; Department of Surgery/Surgical-Oncology, University of California Los Angeles, Los Angeles, California, United States of America.
  • Menjivar JC; Department of Surgery/Surgical-Oncology, University of California Los Angeles, Los Angeles, California, United States of America.
  • Wei B; Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
  • Lucey GM; Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
  • Mareninov S; Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
  • Chen Z; Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
  • Liau LM; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California, United States of America; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
  • Lai A; Department of Neurology/Neuro-Oncology, University of California Los Angeles, Los Angeles, California, United States of America; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
  • Nelson SF; Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America; Jonsson Comprehensive Cancer Center, David
  • Cloughesy TF; Department of Neurology/Neuro-Oncology, University of California Los Angeles, Los Angeles, California, United States of America; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
  • Tso CL; Department of Surgery/Surgical-Oncology, University of California Los Angeles, Los Angeles, California, United States of America; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One ; 10(10): e0141334, 2015.
Article en En | MEDLINE | ID: mdl-26506620
ABSTRACT
Glioblastoma stem cells (GSC) co-exhibiting a tumor-initiating capacity and a radio-chemoresistant phenotype, are a compelling cell model for explaining tumor recurrence. We have previously characterized patient-derived, treatment-resistant GSC clones (TRGC) that survived radiochemotherapy. Compared to glucose-dependent, treatment-sensitive GSC clones (TSGC), TRGC exhibited reduced glucose dependence that favor the fatty acid oxidation pathway as their energy source. Using comparative genome-wide transcriptome analysis, a series of defense signatures associated with TRGC survival were identified and verified by siRNA-based gene knockdown experiments that led to loss of cell integrity. In this study, we investigate the prognostic value of defense signatures in glioblastoma (GBM) patients using gene expression analysis with Probeset Analyzer (131 GBM) and The Cancer Genome Atlas (TCGA) data, and protein expression with a tissue microarray (50 GBM), yielding the first TRGC-derived prognostic biomarkers for GBM patients. Ribosomal protein S11 (RPS11), RPS20, individually and together, consistently predicted poor survival of newly diagnosed primary GBM tumors when overexpressed at the RNA or protein level [RPS11 Hazard Ratio (HR) = 11.5, p<0.001; RPS20 HR = 4.5, p = 0.03; RPS11+RPS20 HR = 17.99, p = 0.001]. The prognostic significance of RPS11 and RPS20 was further supported by whole tissue section RPS11 immunostaining (27 GBM; HR = 4.05, p = 0.01) and TCGA gene expression data (578 primary GBM; RPS11 HR = 1.19, p = 0.06; RPS20 HR = 1.25, p = 0.02; RPS11+RPS20 HR = 1.43, p = 0.01). Moreover, tumors that exhibited unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) or wild-type isocitrate dehydrogenase 1 (IDH1) were associated with higher RPS11 expression levels [corr (IDH1, RPS11) = 0.64, p = 0.03); [corr (MGMT, RPS11) = 0.52, p = 0.04]. These data indicate that increased expression of RPS11 and RPS20 predicts shorter patient survival. The study also suggests that TRGC are clinically relevant cells that represent resistant tumorigenic clones from patient tumors and that their properties, at least in part, are reflected in poor-prognosis GBM. The screening of TRGC signatures may represent a novel alternative strategy for identifying new prognostic biomarkers.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteínas Ribosómicas / Biomarcadores de Tumor / Glioblastoma Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteínas Ribosómicas / Biomarcadores de Tumor / Glioblastoma Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos