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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Comparison of microRNA expression levels between initial and recurrent glioblastoma specimens
Aysegül Ilhan-Mutlu1, Adelheid Wöhrer, Anna Sophie Berghoff
1Department of Medicine I/Oncology, Medical University of Vienna, Vienna, Austria.
Abstract:
Glioblastoma is the most frequent primary brain tumour in adults. Recent therapeutic advances increased patient's survival, but tumour recurrence inevitably occurs. The pathobiological mechanisms involved in glioblastoma recurrence are still unclear. MicroRNAs are small RNAs proposed o have important roles for cancer including proliferation, aggressiveness and metastases development. There exist only few data on the involvement of microRNAs in glioblastoma recurrence. We selected the following 7 microRNAs with potential relevance for glioblastoma pathobiology by means of a comprehensive literature search: microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195, microRNA-221 and microRNA-222. We further selected 15 primary glioblastoma patients, of whom formalin fixed and paraffin embedded tissue (FFPE) of the initial and recurrence surgery were available. All patients had received first line treatment consisting of postoperative combined radiochemotherapy with temozolomide (n = 15). Non-neoplastic brain tissue samples from 3 patients with temporal lobe epilepsy served as control. The expression of the microRNAs were analysed by RT-qPCR. These were correlated with each other and with clinical parameters. All microRNAs showed detectable levels of expressions in glioblastoma group, whereas microRNA-10b was not detectable in epilepsy patients. MicroRNAs except microRNA-21 showed significantly higher levels in epilepsy patients when compared to the levels of first resection of glioblastoma. Comparison of microRNA levels between first and second resections revealed no significant change. Cox regression analyses showed no significant association of microRNA expression levels in the tumor tissue with progression free survival times. Expression levels of microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195, microRNA-221 and microRNA-222 do not differ significantly between initial and recurrent glioblastoma.
Insights
This study investigated microRNA expression in recurrent glioblastoma, finding no significant differences between initial and recurrent tumors. These microRNAs do not appear to be key drivers of glioblastoma recurrence or progression-free survival.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma is the most common primary brain tumor in adults, with recurrence being a significant challenge.
- MicroRNAs (miRNAs) are implicated in cancer progression, but their role in glioblastoma recurrence is not well understood.
- Limited data exists on specific miRNA involvement in glioblastoma recurrence.
Purpose of the Study:
- To investigate the expression levels of seven selected microRNAs in primary and recurrent glioblastoma tissues.
- To determine if there are significant differences in microRNA expression between initial and recurrent glioblastoma.
- To explore the association between microRNA expression and progression-free survival in glioblastoma patients.
Main Methods:
- Literature search identified seven relevant microRNAs: miR-10b, miR-21, miR-181b, miR-181c, miR-195, miR-221, and miR-222.
- RT-qPCR was used to analyze miRNA expression in formalin-fixed, paraffin-embedded (FFPE) tissues from 15 glioblastoma patients (initial and recurrent) and 3 epilepsy patients (control).
- Statistical analyses, including Cox regression, were performed to correlate miRNA levels with clinical parameters and survival.
Main Results:
- All seven microRNAs were detectable in glioblastoma tissues; miR-10b was not detected in epilepsy controls.
- Most microRNAs (except miR-21) showed higher levels in epilepsy patients compared to initial glioblastoma.
- No significant differences in the expression levels of the studied microRNAs were found between initial and recurrent glioblastoma tissues.
- MicroRNA expression levels did not show a significant association with progression-free survival.
Conclusions:
- The investigated microRNAs (miR-10b, miR-21, miR-181b, miR-181c, miR-195, miR-221, miR-222) do not significantly differ between initial and recurrent glioblastoma.
- These specific microRNAs are unlikely to be major drivers of glioblastoma recurrence or progression.
- Further research is needed to elucidate the pathobiological mechanisms underlying glioblastoma recurrence.
