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tRNA-Derived Fragments (tRFs) in Bladder Cancer: Increased 5'-tRF-LysCTT Results in Disease Early Progression and Patients' Poor Treatment Outcome

Citation:

Papadimitriou MA, Avgeris M, Levis P, Papasotiriou EC, Kotronopoulos G, Stravodimos K, Scorilas A. tRNA-Derived Fragments (tRFs) in Bladder Cancer: Increased 5'-tRF-LysCTT Results in Disease Early Progression and Patients' Poor Treatment Outcome. Cancers (Basel) 2020;12

Abstract:

The heterogeneity of bladder cancer (BlCa) prognosis and treatment outcome requires the elucidation of tumors' molecular background towards personalized patients' management. tRNA-derived fragments (tRFs), although originally considered as degradation debris, represent a novel class of powerful regulatory non-coding RNAs. In silico analysis of the TCGA-BLCA project highlighted 5'-tRF-LysCTT to be significantly deregulated in bladder tumors, and 5'-tRF-LysCTT levels were further quantified in our screening cohort of 230 BlCa patients. Recurrence and progression for non-muscle invasive (NMIBC) patients, as well as progression and patient's death for muscle-invasive (MIBC) patients, were used as clinical endpoint events. TCGA-BLCA were used as validation cohort. Bootstrap analysis was performed for internal validation and the clinical net benefit of 5'-tRF-LysCTT on disease prognosis was assessed by decision curve analysis. Elevated 5'-tRF-LysCTT was associated with unfavorable disease features, and significant higher risk for early progression (multivariate Cox: HR = 2.368; p = 0.033) and poor survival (multivariate Cox: HR = 2.151; p = 0.032) of NMIBC and MIBC patients, respectively. Multivariate models integrating 5'-tRF-LysCTT with disease established markers resulted in superior risk-stratification specificity and positive prediction of patients' progression. In conclusion, increased 5'-tRF-LysCTT levels were strongly associated with adverse disease outcome and improved BlCa patients' prognostication.

Notes:

Papadimitriou, Maria-AlexandraAvgeris, MargaritisLevis, PanagiotisPapasotiriou, Evangelia ChKotronopoulos, GeorgiosStravodimos, KonstantinosScorilas, AndreasengT2EDK-02196/This research has been co-financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH - CREATE - INNOVATE (projSwitzerland2020/12/10 06:00Cancers (Basel). 2020 Dec 6;12(12). pii: cancers12123661. doi: 10.3390/cancers12123661.