title: A mesenchymal glioma stem cell profile is related to clinical outcome.
abstract: Recent studies have demonstrated a relationship between the expression of stem cell-associated genes and relapses in glioblastoma (GBM), suggesting a key role for tumor stem cells in this process. Although there is increasing interest in this field, glioma stem cells (GSCs) are still poorly characterized, their 'stemness' state and factors maintaining these properties remain largely unknown. We performed an expression profiling analysis of pluripotency in gliomaspheres derived from 11 patients. Comparative analysis between GSCs and H1 and H9 human embryonic stem cells as well as H9-derived neural stem cells indicates major variations in gene expression of pluripotency factors Nanog and OCT4, but a stable pattern for SOX2 suggesting its important function in maintaining pluripotency in GSCs. Our results also showed that all GSC lines have the capacity to commit to neural differentiation and express mesenchymal or endothelial differentiation markers. In addition, hierarchical clustering analysis revealed two groups of GSCs reflecting their heterogeneity and identified COL1A1 and IFITM1 as the most discriminating genes. Similar patterns have been observed in tumors from which gliomaspheres have been established. To determine whether this heterogeneity could be clinically relevant, the expression of both genes was further analyzed in an independent cohort of 30 patients with GBM and revealed strong correlation with overall survival. In vitro silencing of COL1A1 and IFTM1 confirmed the effect of these mesenchymal-associated genes on cell invasion and gliomasphere initiation. Our results indicate that COL1A1 and IFITM1 genes could be considered for use in stratifying patients with GBM into subgroups for risk of recurrence at diagnosis, as well as for prognostic and therapeutic evolution.
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, INSERM, U935, Poitiers, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, University of Poitiers, U935, Poitiers, France [3] Department of Oncology and Hematology, University Hospital of Poitiers, Poitiers, France.
authors.forename: A
authors.initials: A
authors.lastname: Balbous
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, INSERM, U935, Poitiers, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, University of Poitiers, U935, Poitiers, France [3] Department of Oncology and Hematology, University Hospital of Poitiers, Poitiers, France.
authors.forename: U
authors.initials: U
authors.lastname: Cortes
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, INSERM, U935, Poitiers, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, University of Poitiers, U935, Poitiers, France [3] Department of Oncology and Hematology, University Hospital of Poitiers, Poitiers, France.
authors.forename: K
authors.initials: K
authors.lastname: Guilloteau
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, INSERM, U935, Poitiers, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, University of Poitiers, U935, Poitiers, France [3] Department of Oncology and Hematology, University Hospital of Poitiers, Poitiers, France.
authors.forename: C
authors.initials: C
authors.lastname: Villalva
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, University of Paris Sud 11, U935, Villejuif, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, Paul Brousse-AP-HP Hospital, U935, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Flamant
authors.affiliation: 1] Experimental and Clinical Neurosciences Laboratory, INSERM, U1084, Poitiers, France [2] Experimental and Clinical Neurosciences Laboratory, University of Poitiers, U1084, Poitiers, France.
authors.forename: A
authors.initials: A
authors.lastname: Gaillard
authors.affiliation: Department of Pathology, University Hospital of Poitiers, Poitiers, France.
authors.forename: S
authors.initials: S
authors.lastname: Milin
authors.affiliation: Department of Neurosurgery, University Hospital of Poitiers, Poitiers, France.
authors.forename: M
authors.initials: M
authors.lastname: Wager
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, INSERM, U935, Poitiers, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, University of Poitiers, U935, Poitiers, France [3] Department of Oncology and Hematology, University Hospital of Poitiers, Poitiers, France.
authors.forename: N
authors.initials: N
authors.lastname: Sorel
authors.affiliation: INSERM, CIC 0802, Poitiers, France.
authors.forename: J
authors.initials: J
authors.lastname: Guilhot
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, University of Paris Sud 11, U935, Villejuif, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, Paul Brousse-AP-HP Hospital, U935, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Bennaceur-Griscelli
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, University of Paris Sud 11, U935, Villejuif, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, Paul Brousse-AP-HP Hospital, U935, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Turhan
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, INSERM, U935, Poitiers, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, University of Poitiers, U935, Poitiers, France [3] Department of Oncology and Hematology, University Hospital of Poitiers, Poitiers, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Chomel
authors.affiliation: 1] Malignant and Therapeutic Stem Cell Models Laboratory, INSERM, U935, Poitiers, France [2] Malignant and Therapeutic Stem Cell Models Laboratory, University of Poitiers, U935, Poitiers, France [3] Department of Oncology and Hematology, University Hospital of Poitiers, Poitiers, France.
authors.forename: L
authors.initials: L
authors.lastname: Karayan-Tapon