High expression of cathepsin B and plasminogen activator inhibitor type-1 are strong predictors of survival in glioblastomas.
In contrast to pilocytic astrocytomas (WHO grade I gliomas) that are circumscribed and cured by surgical resection, invasion is a hallmark of grades II-IV gliomas. Proteases play a major role in the invasion process and correlations between glioma grading, survival and protease expression have been demonstrated. In this study, we have chosen to study using different technical approaches (Q-RT-PCR, in situ hybridization and immunohistochemistry) the expression of five molecules involved in extracellular matrix degradation (cathepsin B, MMP2, MMP9, uPA and PAI-1) in glioblastomas in order to determine their prognostic impact among grade IV gliomas. Pilocytic astrocytomas were used as controls. Q-RT-PCR showed that transcripts of uPA, PAI-1, cathepsin B and MMP9 were significantly more expressed in glioblastomas (n = 52), in comparison to pilocytic astrocytomas (n = 17) (P = 0.049, P < 0.0001, P = 0.03 and P < 0.0001, respectively). On both univariate and multivariate analyses, cathepsin B and PAI-1 were strong predictors of overall survival among the group of glioblastomas (P < 0.0001 and P = 0.01, respectively). Immunohistochemical expression of cathepsin B further confirmed its prognostic value in an independent cohort of patients with glioblastoma. In situ hybridization showed that uPA is detected at the invasive edge of glioblastomas, whereas PAI-1 is more abundant in microvascular proliferation and pseudo-palisading cells than at the infiltrative edges. These results suggest that cathepsin B and PAI-1 are important biomarkers for the stratification of glioblastoma patients with respect to survival.
INSERM U911, Centre de Recherche en Oncologie et Oncopharmacologie (CRO2), Angiogenèse, Invasivité et Microenvironnement Tumoral, Faculté de Médecine Timone, 27, Bd Jean Moulin, 13005, Marseille, France.
Carole
C
Colin
Brigitte
B
Voutsinos-Porche
Isabelle
I
Nanni
Frédéric
F
Fina
Philippe
P
Metellus
Dominique
D
Intagliata
Nathalie
N
Baeza
Corinne
C
Bouvier
Christine
C
Delfino
Anderson
A
Loundou
Olivier
O
Chinot
Tamara
T
Lah
Janko
J
Kos
Pierre-Marie
PM
Martin
L'Houcine
L
Ouafik
Dominique
D
Figarella-Branger
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality; D002401:Cathepsin B / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D002401:Cathepsin B