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Circulating MACC1 Transcripts in Glioblastoma Patients Predict Prognosis and Treatment Response.

Authors
  • Hagemann, Carsten1
  • Neuhaus, Nikolas2
  • Dahlmann, Mathias3, 4
  • Kessler, Almuth F5
  • Kobelt, Dennis6, 7
  • Herrmann, Pia8
  • Eyrich, Matthias9
  • Freitag, Benjamin10
  • Linsenmann, Thomas11
  • Monoranu, Camelia M12
  • Ernestus, Ralf-Ingo13
  • Löhr, Mario14
  • Stein, Ulrike15, 16
  • 1 Tumorbiology Laboratory, Department of Neurosurgery, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany. [email protected] , (Germany)
  • 2 Tumorbiology Laboratory, Department of Neurosurgery, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany. [email protected] , (Germany)
  • 3 Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, D-13125 Berlin, Germany. [email protected] , (Germany)
  • 4 German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. [email protected] , (Germany)
  • 5 Tumorbiology Laboratory, Department of Neurosurgery, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany. [email protected] , (Germany)
  • 6 Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, D-13125 Berlin, Germany. [email protected] , (Germany)
  • 7 German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. [email protected] , (Germany)
  • 8 Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, D-13125 Berlin, Germany. [email protected] , (Germany)
  • 9 Department of Pediatric Hematology/Oncology, University Children's Hospital, University of Würzburg, D-97080 Würzburg, Germany. [email protected] , (Germany)
  • 10 Department of Pediatric Hematology/Oncology, University Children's Hospital, University of Würzburg, D-97080 Würzburg, Germany. [email protected] , (Germany)
  • 11 Tumorbiology Laboratory, Department of Neurosurgery, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany. [email protected] , (Germany)
  • 12 Department of Neuropathology, Institute of Pathology, University of Würzburg, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany. [email protected] , (Germany)
  • 13 Tumorbiology Laboratory, Department of Neurosurgery, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany. [email protected] , (Germany)
  • 14 Tumorbiology Laboratory, Department of Neurosurgery, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany. [email protected] , (Germany)
  • 15 Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, D-13125 Berlin, Germany. [email protected] , (Germany)
  • 16 German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. [email protected] , (Germany)
Type
Published Article
Journal
Cancers
Publisher
MDPI AG
Publication Date
Jun 13, 2019
Volume
11
Issue
6
Identifiers
DOI: 10.3390/cancers11060825
PMID: 31200581
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Glioblastoma multiforme is the most aggressive primary brain tumor of adults, but lacks reliable and liquid biomarkers. We evaluated circulating plasma transcripts of metastasis-associated in colon cancer-1 (MACC1), a prognostic biomarker for solid cancer entities, for prediction of clinical outcome and therapy response in glioblastomas. MACC1 transcripts were significantly higher in patients compared to controls. Low MACC1 levels clustered together with other prognostically favorable markers. It was associated with patients' prognosis in conjunction with the isocitrate dehydrogenase (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 (median OS 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 levels receiving standard therapy survived longer (median OS 22.6 months) than patients with high MACC1 levels (median OS 8.1 months). Patients not receiving the standard regimen showed the worst prognosis, independent of MACC1 levels (low: 6.8 months, high: 4.4 months). Addition of circulating MACC1 transcript levels to the existing prognostic workup may improve the accuracy of outcome prediction and help define more precise risk categories of glioblastoma patients.

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