tRNA-Derived Fragments (tRFs) in Bladder Cancer: Increased 5′-tRF-LysCTT Results in Disease Early Progression and Patients’ Poor Treatment Outcome
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. In Silico Analysis of tRFs in Bladder Tumors—Functional Analysis of 5′-tRF-LysCTT
2.2. Baseline Clinical and Experimental Data
2.3. 5′-tRF-LysCTT Levels are Associated with Unfavorable Prognostic Features of BlCa
2.4. NMIBC (TaT1) Patients with Elevated 5′-tRF-LysCTT are at Significantly Higher Risk for Short-Term Progression to Muscle-Invasive Disease Stage
2.5. Increased 5′-tRF-LysCTT Levels Are Associated with Progression and Shorter Overall Survival of MIBC Patients
2.6. The Evaluation of 5′-tRF-LysCTT Levels Improves the Prognostic Significance of BlCa Established Clinical Markers
2.7. Decision Curve Analysis Revealed the Superior Clinical Net Benefit in Disease Prognosis by Multivariate Models Incorporating 5′-tRF-LysCTT
3. Discussion
4. Materials and Methods
4.1. Screening Cohort
4.2. Validation Cohort
4.3. Gene Ontology (GO) Enrichment Analysis
4.4. Extraction and Polyadenylation of Total RNA
4.4.1. Tissue Samples
4.4.2. Serum Samples
4.4.3. First-Strand cDNA Synthesis
4.4.4. Quantitative Real-Time PCR (qPCR)
4.4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Variable | No. of Patients |
---|---|
n = 230 | |
Disease | |
NMIBC (Ta, T1) | 141 (61.3%) |
MIBC (T2-T4) | 89 (38.7%) |
Tumor stage | |
pTa | 76 (33.0%) |
pT1 | 65 (28.3%) |
pT2 | 39 (17.0%) |
pT3 | 33 (14.3%) |
pT4 | 17 (7.4%) |
Grade (WHO 2004) | |
Low | 87 (37.8%) |
High | 143 (62.2%) |
Grade (WHO 1973) | |
1 | 25 (10.9%) |
2 | 79 (34.3%) |
3 | 126 (54.8%) |
Gender | |
Male | 188 (81.7%) |
Female | 42 (18.3%) |
Non-muscle invasive bladder cancer (NMIBC; TaT1) | |
EORTC risk group | |
Low risk | 22 (13.2%) |
Intermediate risk | 45 (32.2%) |
High risk | 74 (54.5%) |
Disease monitoring | |
Follow-up patients | 130 |
Recurrence/Progression | 53 (40.8%)/28 (21.5%) |
Event-free survival | 77 (59.2%)/102 (78.5%) |
Excluded from follow-up | 11 |
Muscle-invasive bladder cancer (MIBC; T2-T4) | |
Disease monitoring | |
Follow-up patients | 75 |
Progression-free survival/Alive | 32 (42.7%)/38 (50.7%) |
Progression/Death | 43 (57.3%) 37 (49.3%) |
Excluded from follow-up | 14 |
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Papadimitriou, M.-A.; Avgeris, M.; Levis, P.; Papasotiriou, E.C.; 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 2020, 12, 3661. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12123661
Papadimitriou M-A, 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. 2020; 12(12):3661. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12123661
Chicago/Turabian StylePapadimitriou, Maria-Alexandra, Margaritis Avgeris, Panagiotis Levis, Evangelia Ch. Papasotiriou, Georgios Kotronopoulos, Konstantinos Stravodimos, and Andreas Scorilas. 2020. "tRNA-Derived Fragments (tRFs) in Bladder Cancer: Increased 5′-tRF-LysCTT Results in Disease Early Progression and Patients’ Poor Treatment Outcome" Cancers 12, no. 12: 3661. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12123661