1066 - Multi-Omics Analyses of Biological Difference between Photon and Proton Irradiation on Glioblastoma Organoids
Presenter(s)
J. Zhao, J. Chen, Y. Lin, and H. Liu; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Purpose/Objective(s): To elucidate the unique biological responses of proton irradiation compared to photon irradiation on glioblastoma organoids and to identify potential serum biomarkers and radiosensitizing targets.
Materials/Methods: Optimal irradiation dose was determined for both photon and proton irradiation in the T98G glioblastoma cell line using comet assays and DNA damage and repair markers (?-H2AX, p-p53). Next, to compare the effects of proton and photon irradiation on tumor progression by measuring tumor volume and survival time in orthotopic glioblastoma xenograft models following photon and proton irradiation. Finally, patient-derived glioblastoma organoids (GBOs) were exposed to either photon or proton irradiation. Transcriptomic changes were assessed at 2 hours post-irradiation, while proteomic, metabolomic, and phosphoproteomic changes were assessed at 24 hours post-irradiation.
Results: Proton irradiation induced 6133 unique gene expression changes in GBOs compared to 2944 changes observed following photon irradiation. These proton-specific alterations of mRNA were enriched in Parkinson’s disease and Huntington’s disease pathways. Similarly, proton irradiation resulted in 517 unique protein expression changes compared to 262 changes after photon irradiation. These proton-specific alterations of proton were enriched in ECM-receptor interaction and focal adhesion pathways. Interestingly, phosphoproteomic analysis revealed that phosphorylated proteins after proton irradiation were also enriched in this two pathways. Finally, proton irradiation resulted in 56 unique metabolics change compared to 51 metabolics change after photon irradiation. These unique metabolics were enriched in carbohydrate digestion and absorption and glycine, serine, and threonine metabolism pathways.
Conclusion: Multi-omics analyses revealed that proton irradiation, unlike photon irradiation, elicits unique biological effects in GBOs, which even more complex across transcriptional, proteomic, and metabolomic levels. Further investigation is warranted to identify potential serum biomarkers and radiosensitizing targets.