Abstract
Objectives
This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres.
Methods
We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level.
Results
The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides.
Conclusion
Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.
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Acknowledgements
We would like to extend our heartfelt thanks to Dr. Yaou Liu, who serves as the Head of the Department of Radiology, Beijing Tiantan Hospital, Capital Medical University. His invaluable assistance in acquiring the imaging data was pivotal to the success of our study.
Funding
The National Natural Science Foundation of China (82172028) provided support for the work.
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The conceptual foundation and structural layout of the research were led by JX and ZGH. Contributions to the data interpretation were made by CDY, XYS, GL, and BWX. ZCY was responsible for creating the figures and drafting the manuscript. The research was supervised by ZHD and SJS, who provided critical direction. FCY performed an exhaustive review, adding meaningful advice and recommendations. All contributing authors have examined and endorsed the finalized manuscript and jointly agree to its submission for journal publication.
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Yang, Zc., Yin, Cd., Yeh, Fc. et al. Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis. J Neurooncol 166, 155–165 (2024). https://doi.org/10.1007/s11060-023-04539-5
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DOI: https://doi.org/10.1007/s11060-023-04539-5