Small-RNA Profiling Links 5’-tRNA Halves to Post-therapeutic Disease Persistence and Poor Patient Survival in Glioblastoma
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Glioblastoma (GBM) is a highly lethal brain cancer with limited therapeutic durability, where the majority of patients develop recurrent or persistent disease after standard chemoradiotherapy. Meanwhile, tRNA-derived fragments (tRFs) have become increasingly relevant to cancer biology; however, their clinical relevance in GBM remains undefined. Here, we report that a specific family of tRFs, 5’-tRNA halves (tiR5s) dominates the small RNA landscape of GBM patient tumors and associates with worse overall survival, post-therapeutic disease persistence, and pro-invasive proteogenomic pathways across two independent GBM patient cohorts. This association between elevated tiR5 levels and therapeutic resistance re-emerges in radiation-resistant GBM xenograft models. Our findings reveal that tiR5s are an underappreciated molecular feature of highly aggressive GBM tumors, supporting further investigation into their biological roles and prognostic utility in GBM.
Highlights
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tiR5s are the predominant tRF family in primary GBM patient tumors
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Elevated tiR5 expression distinguishes primary GBM tumors that develop persistent disease after first-line therapy
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Radiation-resistant GBM PDX models show elevated tiR5 expression
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Elevated tiR5 expression associates with poor overall patient survival and pro-invasive molecular programs in GBM patient tumors
