Title:Gamma Knife Radiosurgery Modulates micro-RNA Levels in Patients with
Brain Metastasis
Volume: 16
Issue: 3
Author(s): Imran Khan, Kerime Akdur, Sadaf Mahfooz, Elif Burce Elbasan, Ayten Sakarcan, Busra Karacam, Georges Sinclair, Sahabettin Selek, Fahri Akbas and Mustafa Aziz Hatiboglu*
Affiliation:
- Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University,
Yalıköy St., Beykoz, Istanbul, Turkey
- Department of Neurosurgery, Bezmialem Vakif University Medical School, Vatan
Street, Fatih, Istanbul, Turkey
Keywords:
Brain metastasis, stereotactic radiosurgery, gamma knife radiosurgery, immune response, miRNA, oncogenic miRNAs, tumor-suppressor miRNAs, serum levels.
Abstract:
Background: The relation between micro-RNA (miRNA) modulation and immune cell
activity in high-dose radiation settings is not clearly understood.
Objective: To investigate the role of stereotactic radiosurgery (SRS) in (i) the regulation of tumorsuppressor
and oncogenic miRNAs as well as (ii) its effect on specific immune cell subsets in patients
with metastatic brain tumors (MBT).
Methods: 9 MBT patients who underwent gamma knife-based stereotactic radiosurgery (GKRS)
and 8 healthy individuals were included. Serum samples were isolated at three-time intervals (before
GKRS, 1 hour, and 1-month post-GKRS). Expressions of tumor-suppressor (miR-124) and
oncogenic (miR-21, miR-181a, miR-23a, miR-125b, and miR-17) miRNAs were quantified by
qPCR. The lymphocytic frequency (CD3+, CD4+, CD8+, CD56+, CD19+, and CD16+) was investigated
by means of flow cytometry.
Results: The median age was 64 years (range: 50-73 years). The median prescription dose was
20Gy (range: 16Gy-24Gy), all delivered in a single fraction. The median overall survival and progression-
free survival were 7.8 months (range: 1.7-14.9 months) and 6.7 months (range: 1.1-11.5
months), respectively. Compared to healthy controls, baseline levels of oncogenic miRNAs were
significantly higher, while tumor-suppressing miRNA levels remained markedly lower in MBT
patients prior to GKRS. Following GKRS, there was a reduction in the expression of miR-21,
miR-17, and miR-181a; simultaneously, increased expression increased of miR-124 was observed.
No significant difference in immune cell subsets was noted post GKRSIn a similar fashion. We
noted no correlation between patient characteristics, radiosurgery data, miRNA expression, and
immune cell frequency.
Conclusion: For this specific population with MBT disease, our data suggest that stereotactic radiosurgery
may modulate the expression of circulating tumor-suppressor and oncogenic miRNAs, ultimately
enhancing key anti-tumoral responses. Further evaluation with larger cohorts is warranted.
