High metallothionein predicts poor survival in glioblastoma multiforme.
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.


CONCLUSIONS
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.
Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. ruty.shai@sheba.health.gov.il.
Ruty
R
Mehrian-Shai
Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. michal@droren.co.il.
Michal
M
Yalon
Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Amos.Simon@sheba.health.gov.il.
Amos J
AJ
Simon
Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Eran.Eyal@sheba.health.gov.il.
Eran
E
Eyal
Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. tatipk86@gmail.com.
Tatyana
T
Pismenyuk
Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. itaimoshe@gmail.com.
Itai
I
Moshe
Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel-Aviv, Israel. shlomic@tasmc.health.gov.il.
Shlomi
S
Constantini
Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. amost@post.tau.ac.il.
Amos
A
Toren
D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D008668:Metallothionein