TY  - JOUR
A1  - Feldheim, Jonas
A1  - Kessler, Almuth F
A1  - Schmitt, Dominik
A1  - Wilczek, Lara
A1  - Linsenmann, Thomas
A1  - Dahlmann, Mathias
A1  - Monoranu, Camelia M
A1  - Ernestus, Ralf-Ingo
A1  - Hagemann, Carsten
A1  - Löhr, Mario
T1  - Expression of activating transcription factor 5 (ATF5) is increased in astrocytomas of different WHO grades and correlates with survival of glioblastoma patients
JF  - OncoTargets and Therapy
N2  - Background: 
ATF5 suppresses differentiation of neuroprogenitor cells and is overexpressed in glioblastoma (GBM). A reduction of its expression leads to apoptotic GBM cell death. Data on ATF5 expression in astrocytoma WHO grade II (low-grade astrocytoma [LGA]) are scarce and lacking on recurrent GBM.

Patients and methods: 
ATF5 mRNA was extracted from frozen samples of patients’ GBM (n=79), LGA (n=40), and normal brain (NB, n=10), quantified by duplex qPCR and correlated with retrospectively collected clinical data. ATF5 protein expression was evaluated by measuring staining intensity on immunohistochemistry.

Results: 
ATF5 mRNA was overexpressed in LGA (sevenfold, P<0.001) and GBM (tenfold, P<0.001) compared to NB, which was confirmed on protein level. Although ATF5 mRNA expression in GBM showed a considerable fluctuation range, groups of varying biological behavior, that is, local/multifocal growth or primary tumor/relapse and the tumor localization at diagnosis, were not significantly different. ATF5 mRNA correlated with the patients’ age (r=0.339, P=0.028) and inversely with Ki67-staining (r=-0.421, P=0.007). GBM patients were allocated to a low and a high ATF5 expression group by the median ATF5 overexpression compared to NB. Kaplan–Meier analysis and Cox regression indicated that ATF5 mRNA expression significantly correlated with short-term survival (t<12 months, median survival 18 vs 13 months, P=0.022, HR 2.827) and progression-free survival (PFS) (12 vs 6 months, P=0.024). This advantage vanished after 24 months (P=0.084).

Conclusion: 
ATF5 mRNA expression could be identified as an additional, though not independent factor correlating with overall survival and PFS. Since its inhibition might lead to the selective death of glioma cells, it might serve as a potential ubiquitous therapeutic target in astrocytic tumors.
KW  - glioblastoma multiforme
KW  - recurrence
KW  - growth pattern
KW  - protein and mRNA expression
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177541
VL  - 11
ER  - 
TY  - JOUR
A1  - Hagemann, Carsten
A1  - Neuhaus, Nikolas
A1  - Dahlmann, Mathias
A1  - Kessler, Almuth F.
A1  - Kobelt, Dennis
A1  - Herrmann, Pia
A1  - Eyrich, Matthias
A1  - Freitag, Benjamin
A1  - Linsenmann, Thomas
A1  - Monoranu, Camelia M.
A1  - Ernestus, Ralf-Ingo
A1  - Löhr, Mario
A1  - Stein, Ulrike
T1  - Circulating MACC1 transcripts in glioblastoma patients predict prognosis and treatment response
JF  - Cancers
N2  - Glioblastoma multiforme is the most aggressive primary brain tumor of adults, but lacksreliable and liquid biomarkers. We evaluated circulating plasma transcripts of metastasis-associatedin colon cancer-1 (MACC1), a prognostic biomarker for solid cancer entities, for prediction of clinicaloutcome and therapy response in glioblastomas.  MACC1 transcripts were significantly higher inpatients compared to controls.  Low MACC1 levels clustered together with other prognosticallyfavorable markers.  It was associated with patients’ prognosis in conjunction with the isocitratedehydrogenase (IDH) mutation status: IDH1 R132H mutation and low MACC1 was most favorable(median overall survival (OS) not yet reached), IDH1 wildtype and high MACC1 was worst (medianOS 8.1 months), while IDH1 wildtype and low MACC1 was intermediate (median OS 9.1 months).No patients displayed IDH1 R132H mutation and high MACC1. Patients with low MACC1 levelsreceiving standard therapy survived longer (median OS 22.6 months) than patients with high MACC1levels (median OS 8.1 months).   Patients not receiving the standard regimen showed the worstprognosis, independent of MACC1 levels (low: 6.8 months, high: 4.4 months). Addition of circulatingMACC1 transcript levels to the existing prognostic workup may improve the accuracy of outcomeprediction and help define more precise risk categories of glioblastoma patients.
KW  - metastasis-associated in colon cancer 1 (MACC1)
KW  - glioblastoma multiforme
KW  - liquid biopsy
KW  - therapy response
KW  - prognostic marker
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197327
SN  - 2072-6694
VL  - 11
IS  - 6
ER  -