2095 Transfer RNA Fragments in Patient Plasma Extracellular Vesicles as Biomarkers of High-Grade Glioma

INTRODUCTION: High-grade gliomas (HGG) are universally fatal (with a progression-free survival of 9 months and overall survival of 14 months in the Nova Scotia cohort). Extracellular vesicles (EVs) released into the plasma from the tumor microenvironment (TME) can contribute to a pro-tumorigenic setting. Understanding the contents of these plasma EVs may further our understanding of HGG and potentially reveal novel targets and biomarkers. tRNA fragments are among the most abundant small RNAs contained in EVs and have recently been described as having pro-tumour or anti-tumour effects in cancer. In this study, we present the transfer RNA (tRNA) fragments contained in plasma EVs from 10 HGG patients at diagnosis versus 4 controls. METHODS: EVs were isolated using Vn96 capture from plasma obtained at the time of HGG diagnosis. Small RNA (sRNA) was extracted from the EVs, followed by next-generation sequencing. Subsequent analysis for tRNA fragments was performed utilizing MintMap. Filtering and differential expression were then carried out. RESULTS: Analysis of plasma EVs highlighted distinct differences in tRNA fragments between High-Grade Glioma (HGG) and control samples. HGG EVs exhibited a global reduction in tRNA content, higher 5’ tfRNA proportions, and increased nuclear tfrna compared to controls. Additionally, a notable decrease in the normalized reads of 3' halves in HGG was observed. Interestingly, fragments from tRNA met-CAT displayed significant differential expression between EVs and HGG tissue, suggesting differential sorting and therapeutic potential. CONCLUSIONS: Our study is one of the first comprehensive catalogues of tRNA fragments in HGG and suggests the importance of tRNA fragments as biomarkers and potential therapeutic targets.