Article
Gene expression level of different gene sets varies between de-novo and recurrent grade III glioma
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Authors
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Moritz Perrech
- Labor für Neuroonkologie und Experimentelle Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Universitätsklinikum Köln
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Gabriele Röhn
- Labor für Neuroonkologie und Experimentelle Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Universitätsklinikum Köln
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Roland Goldbrunner
- Labor für Neuroonkologie und Experimentelle Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Universitätsklinikum Köln
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Marco Timmer
- Labor für Neuroonkologie und Experimentelle Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Universitätsklinikum Köln
| Published: | May 13, 2014 |
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Outline
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Objective: Increasing knowledge of the molecular basis of gliomas supports the identification of tumor subgroups that differ in biological behaviour and response to treatment. IDH1 mutation, for example, seems to be crucial in distinguishing primary from secondary glioblastomas. Moreover, two distinct anaplastic astrocytoma subgroups were postulated based on FET-PET data. While one group showed a heterogenous tracer uptake kinetic, the other group had a homogenous tracer uptake profile. However, it remains elusive whether they are distinct tumor subgroups or if the homogenous form has progressed further. In our study, we analysed the expression of different sets of tumor genes in de-novo and recurrent grade III gliomas.
Method: 20 samples of “recurrent grade III gliomas” and 10 samples of “primary grade III gliomas” were obtained from intraoperative specimen. Recurrent glioma patients had a prior history of diffuse glioma whereas primary gliomas were diagnosed de-novo. Tumor samples were snap-frozen and processed for further analysis. Expression levels of different sets of genes were analysed by rtPCR: Primer were used for chemo-resistency genes (CYP1b1, ABCC1, ABCG2, GSTP1), stemness genes (NANOG, KLF4) and growth factor associated genes (FGFR3c).
Results: The majority of genes analysed differed in expression level between primary and recurrent grade III gliomas. From the stemness gene set KLF4 was higher expressed in primary tumors (6.43 ± 1.19) compared to recurrent tumors (3.47 ± 0.58). Moreover, FGFR was significantly higher expressed in primary tumors (23.11 ± 9.56) than in recurrent tumors (5.39 ± 2.93). In the chemoresitancy set, CYP1B1 (1.35 ± 0.46 vs. 0.37 ± 0.09) was higher expressed in primary tumors whereas ABCG2 (0.14 ± 0.03 vs. 0.85 ± 0.36), GSTP1 (1.67 ± 0.54 vs. 3.39 ± 0.7) and ABCC1 (1.8 ± 0.5 vs. 3.8 ± 1.8) were higher expressed in recurrent tumors.
Conclusions: In our study, we found differences in gene expression levels of different gene sets between de-novo diagnosed anaplastic astrocytomas and recurrent anaplastic astrocytomas. Thus, the different groups in tracer uptake kinetics that were found in anaplastic astrocytoma might be based on tumor subgroups showing a distinct gene expression profile. However, our study only analyses a limited number of gene sets.
