High metallothionein predicts poor survival in glioblastoma multiforme

Abstract

Background: Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor. Even with vigorous surgery, radiation and chemotherapy treatment, survival rates of GBM are very poor and predictive markers for prognosis are currently lacking. Methods: We performed whole genome expression studies of 67 fresh frozen untreated GBM tumors and validated results by 210 GBM samples' expression data from The Cancer Genome Atlas. Results and discussion: Here we show that in GBM patients, high metallothionein (MT) expression is associated with poor survival whereas low MT levels correspond to good prognosis. Furthermore we show that in U87 GBM cell line, p53 is found to be in an inactive mutant-like conformation concurrently with more than 4 times higher MT3 expression level than normal astrocytes and U251GBM cell line. We then show that U87-p53 inactivity can be rescued by zinc (Zn). Conclusions: Taken together, these data suggest that MT expression may be a potential novel prognostic biomarker for GBM, and that U87 cells may be a good model for patients with non active WT p53 resulting from high levels of MTs.