Human glioblastoma multiforme (GBM) is an aggressive cancer with a very poor prognosis. Cripto-1 (CR-1) has a key regulatory role in embryogenesis, while in adult tissue re-expression of CR-1 has been correlated to malignant progression in solid cancers of non-neuronal origin. As CR-1 expression has yet to be described in cerebral cancer and CR-1 is regulated by signaling pathways dysregulated in GBM, we aimed to investigate CR-1 in the context of expression in GBM. The study was performed using enzyme-linked immunosorbent assay (ELISA), Western blotting, polymerase chain reaction (PCR) and immunohistochemistry to analyze the blood and tissue from 28 GBM and 4 low-grade glioma patients. Within the patient cohort, we found high CR-1 protein levels in blood plasma to significantly correlate with a shorter overall survival. We identified CR-1 in different areas of GBM tissue, including perivascular tumor cells, and in endothelial cells. Collectively, our data suggest that CR-1 could be a prognostic biomarker for GBM with the potential of being a therapeutic target.

The increasing interest in identifying molecular biomarkers to determine patient prognosis in glioblastoma multiforme (GBM) has resulted in several microRNA (miRNA)-based signatures able to predict progression-free and overall survival. However, the coherency between these signatures is small, and correlations to clinicopathological features other than survival are seldom seen. The aim of this study was to identify any significant relationship between miRNA signatures and clinicopathological data by combining pathological features with miRNA and mRNA analysis in fourteen GBM patients. In total, 161 miRNAs were shown to cluster the GBM tumor samples into long- and short-term-surviving patients. Many of these miRNAs were associated with differential expression in GBM, including a number of miRNAs shown to confer risk or protection with respect to clinical outcome and to modulate the mesenchymal mode of migration and invasion. An inverse relationship between miR-125b and nestin expression was identified and correlated with overall survival in GBM patients, eloquently illustrating how clinicopathological findings and molecular profiling may be a relevant combination to predict patient outcome. The intriguing finding that many of the differentially expressed miRNAs contained exosome-packaging motifs in their mature sequences suggests that we must expand our view to encompass the complex intercellular communication in order to identify molecular prognostic biomarkers and to increase our knowledge in the field of GBM pathogenesis.

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