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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

Authors: Thomas Urup, Line Mærsk Staunstrup, Signe Regner Michaelsen, Kristoffer Vitting-Seerup, Marc Bennedbæk, Anders Toft, Lars Rønn Olsen, Lars Jønson, Shohreh Issazadeh-Navikas, Helle Broholm, Petra Hamerlik, Hans Skovgaard Poulsen, Ulrik Lassen

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Bevacizumab combined with chemotherapy produces clinical durable response in 25–30% of recurrent glioblastoma patients. This group of patients has shown improved survival and quality of life. The aim of this study was to investigate changes in gene expression associated with response and resistance to bevacizumab combination therapy.

Methods

Recurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.

Results

By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non-responders 1 gene was significantly differentially expressed. In responders, this approach revealed 256 significantly differentially expressed genes (72 down- and 184 up-regulated genes at the time of progression). Genes differentially expressed in responders revealed a shift towards a more proneural and less mesenchymal phenotype at the time of progression.

Conclusions

Bevacizumab combination treatment demonstrated a significant impact on the transcriptional changes in responders; but only minimal changes in non-responders. This suggests that non-responding glioblastomas progress chaotically without following distinct gene expression changes while responding tumors adaptively respond or progress by means of the same transcriptional changes. In conclusion, we hypothesize that the identified gene expression changes of responding tumors are associated to bevacizumab response or resistance mechanisms.
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Metadata
Title
Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients
Authors
Thomas Urup
Line Mærsk Staunstrup
Signe Regner Michaelsen
Kristoffer Vitting-Seerup
Marc Bennedbæk
Anders Toft
Lars Rønn Olsen
Lars Jønson
Shohreh Issazadeh-Navikas
Helle Broholm
Petra Hamerlik
Hans Skovgaard Poulsen
Ulrik Lassen
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3251-3

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