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69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

03.06. - 06.06.2018, Münster

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Plasma levels of circulating MACC1 transcripts cosegregate with other prognostic markers and treatment response in glioblastoma patients

Meeting Abstract

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  • Carsten Hagemann - Universitätsklinikum Würzburg, Klinik für Neurochirurgie, Tumorbiologie, Würzburg, Deutschland
  • Nikolas Neuhaus - Universitätsklinikum Würzburg, Klinik für Neurochirurgie, Tumorbiologie, Würzburg, Deutschland
  • Mathias Dahlmann - Charité - Universitätsmedizin Berlin, Berlin, Deutschland; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Heidelberg, Deutschland
  • Almuth F. Kessler - Universitätsklinikum Würzburg, Klinik für Neurochirurgie, Tumorbiologie, Würzburg, Deutschland
  • Dennis Kobelt - Charité - Universitätsmedizin Berlin, Berlin, Deutschland; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Heidelberg, Deutschland
  • Pia Herrmann - Charité - Universitätsmedizin Berlin, Berlin, Deutschland
  • Matthias Eyrich - Universitätsklinikum Würzburg, Klinik für pädiatrische Hämatoonkologie, Würzburg, Deutschland
  • Benjamin Freitag - Universitätsklinikum Würzburg, Klinik für pädiatrische Hämatoonkologie, Würzburg, Deutschland
  • Camelia M. Monoranu - Universitätsklinikum Würzburg, Abteilung für Neuropathologie, Würzburg, Deutschland
  • Ralf-Ingo Ernestus - Universitätsklinikum Würzburg, Klinik für Neurochirurgie, Tumorbiologie, Würzburg, Deutschland
  • Mario Löhr - Universitätsklinikum Würzburg, Klinik für Neurochirurgie, Tumorbiologie, Würzburg, Deutschland
  • Ulrike Stein - Charité - Universitätsmedizin Berlin, Berlin, Deutschland; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Heidelberg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie. Münster, 03.-06.06.2018. Düsseldorf: German Medical Science GMS Publishing House; 2018. DocP091

doi: 10.3205/18dgnc432, urn:nbn:de:0183-18dgnc4322

Veröffentlicht: 18. Juni 2018

© 2018 Hagemann et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

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Objective: IDH1-mutation and MGMT-promoter methylation are established prognostic markers in Glioblastoma multiforme (GBM). However, invasive procedures are needed to obtain the required tumor tissue. Metastasis-associated in colon cancer-1 (MACC1) can easily be measured in peripheral blood and has been established as a prognostic plasma marker for several solid cancer entities. Here, we evaluated whether circulating MACC1 transcripts could be useful to predict response to therapy and clinical outcome in GBM.

Methods: Plasma samples were collected from 45 GBM patients (31 IDH1 wildtype (wt), 5 IDH1R132H, 9 unspecified) before surgery. Samples from 15 healthy volunteers served as controls. MACC1-transcript levels, determined by qRT-PCR, were correlated with patient overall survival (OS) and clinical data of known prognostic significance. Cut-off values for Kaplan-Meier analyses were determined by ROC calculations. Cluster analyses were performed.

Results: MACC1 transcripts were higher in plasma of GBM patients compared to healthy controls (P<0.0001), yet differentially distributed within the cohort. Low MACC1 levels clustered together with all other favorable markers, i.e. small tumor volume, young age, IDH1R132H and MGMT promoter methylation. MACC1 levels correlated with patient prognosis in conjunction with the IDH mutation status: patients with IDH1R132H mutation and low MACC1 levels showed the most favorable outcome (mean OS 54.0 months (m), SD=9.8; 95% CI 34.7-73.3), those with IDH1wt and high MACC1 had the worst prognosis (mean OS 10.5 m), while those with IDH1wt and low MACC1 were intermediate (mean OS 20.3 m). No patients in this cohort displayed IDH1R132H and high MACC1 expression. Interestingly, patients with low MACC1 levels receiving standard therapy (operation and radiochemotherapy according to Stupp) (n=29) survived longest (mean OS 36.9 m, SD=6.5; 95% CI 24.1-49.7). Patients with high MACC1 showed shorter OS (mean OS 13.0 m). The worst prognosis had patients not receiving the standard regimen (n=16), independently of their MACC1 levels (MACC1 low: 5.2 m; MACC1 high: 5.5 m).

Conclusion: The inclusion of circulating MACC1 transcript levels into the diagnostic workup might improve the accuracy of outcome prediction and thus help to define more precise risk categories of GBM patients. Whether pharmaceutical inhibition of MACC1 expression might be of general benefit for the treatment response and survival of GBM patients remains to be determined.