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Updated: Jun 9, 2026
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line
François Ducray1, Aurélien de Reyniès, Olivier Chinot
1INSERM, U842, Lyon, F-69372 France. francois.ducray@chu-lyon.fr
Background:
The molecular characteristics associated with the response to treatment in glioblastomas (GBMs) remain largely unknown. We performed a retrospective study to assess the genomic characteristics associated with the response of GBMs to either first-line chemotherapy or radiation therapy. The gene expression (n = 56) and genomic profiles (n = 67) of responders and non-responders to first-line chemotherapy or radiation therapy alone were compared on Affymetrix Plus 2 gene expression arrays and BAC CGH arrays.
Results:
According to Verhaak et al.'s classification system, mesenchymal GBMs were more likely to respond to radiotherapy than to first-line chemotherapy, whereas classical GBMs were more likely to respond to first-line chemotherapy than to radiotherapy. In patients treated with radiation therapy alone, the response was associated with differential expression of microenvironment-associated genes; the expression of hypoxia-related genes was associated with short-term progression-free survival (< 5 months), whereas the expression of immune genes was associated with prolonged progression-free survival (> 10 months). Consistently, infiltration of the tumor by both CD3 and CD68 cells was significantly more frequent in responders to radiotherapy than in non-responders. In patients treated with first-line chemotherapy, the expression of stem-cell genes was associated with resistance to chemotherapy, and there was a significant association between response to treatment and p16 locus deletions. Consistently, in an independent data set of patients treated with either radiotherapy alone or with both radiotherapy and adjuvant chemotherapy, we found that patients with the p16 deletion benefited from adjuvant chemotherapy regardless of their MGMT promoter methylation status, whereas in patients without the p16 deletion, this benefit was only observed in patients with a methylated MGMT promoter.
Conclusion:
Differential expression of microenvironment genes and p16 locus deletion are associated with responses to radiation therapy and to first-line chemotherapy, respectively, in GBM. Recently identified transcriptomic subgroups of GBMs seem to respond differently to radiotherapy and to first-line chemotherapy.
Insights
Molecular features predict glioblastoma treatment response. Mesenchymal tumors respond better to radiation, while classical tumors favor chemotherapy, with specific gene expressions and p16 deletions indicating differential treatment efficacy.
Area of Science:
- Neuro-oncology
- Genomics
- Molecular Biology
Background:
- Glioblastoma (GBM) treatment response is poorly understood at the molecular level.
- Retrospective analysis of genomic and gene expression profiles in GBM patients.
Purpose of the Study:
- To identify molecular characteristics associated with treatment response in GBM.
- To compare genomic profiles of responders versus non-responders to chemotherapy or radiation therapy.
Main Methods:
- Gene expression analysis (n=56) using Affymetrix Plus 2 arrays.
- Genomic profiling (n=67) using BAC CGH arrays.
- Comparison of responders and non-responders to first-line chemotherapy or radiation therapy alone.
Main Results:
- Mesenchymal GBMs responded better to radiotherapy; classical GBMs responded better to chemotherapy.
- Radiation response linked to microenvironment genes (hypoxia, immune cells); chemotherapy response linked to stem-cell genes and p16 locus deletions.
- p16 deletion predicted benefit from adjuvant chemotherapy, irrespective of MGMT methylation status.
Conclusions:
- Differential expression of microenvironment genes and p16 locus deletion are key indicators for GBM response to radiation and chemotherapy, respectively.
- GBM transcriptomic subgroups exhibit distinct responses to radiotherapy and chemotherapy.
