Plasma tRNA Fragments Derived from 5′ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer

Wang, Jingyi; Ma, Ge; Li, Minghui; Han, Xu; Xu, Jin; Liang, Mengdi; Mao, Xiao‐Ming; Chen, Xiang; Xia, Tiansong; Li, Xiaoan; Wang, Shui

doi:10.1016/j.omtn.2020.07.026

Cited by 47 publications

(37 citation statements)

References 48 publications

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“…With independence on the mechanism of release, stability, and possible biological activity, it is worth mentioning that the high abundance of tRFs in biofluids has opened an active field of research in biomarker discovery. The biogenesis of stress linked tRFs is reflected in plasma, with altered profiles in diseases such as cancer ( Dhahbi et al, 2014 ; Wang et al, 2020 ) or epilepsy ( Hogg et al, 2019 ). This highlights the need to include these species in the definition of prognostic and/or diagnostic biosignatures.…”

Section: Discussionmentioning

confidence: 99%

Toward an Understanding of Extracellular tRNA Biology

Torres

Martı́

2021

Front. Mol. Biosci.

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Extracellular RNAs (exRNAs) including abundant full length tRNAs and tRNA fragments (tRFs) have recently garnered attention as a promising source of biomarkers and a novel mediator in cell-to-cell communication in eukaryotes. Depending on the physiological state of cells, tRNAs/tRFs are released to the extracellular space either contained in extracellular vesicles (EVs) or free, through a mechanism that is largely unknown. In this perspective article, we propose that extracellular tRNAs (ex-tRNAs) and/or extracellular tRFs (ex-tRFs) are relevant paracrine signaling molecules whose activity depends on the mechanisms of release by source cells and capture by recipient cells. We speculate on how ex-tRNA/ex-tRFs orchestrate the effects in target cells, depending on the type of sequence and the mechanisms of uptake. We further propose that tRNA modifications may be playing important roles in ex-tRNA biology.

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Section: Discussionmentioning

confidence: 99%

Toward an Understanding of Extracellular tRNA Biology

Torres

Martı́

2021

Front. Mol. Biosci.

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“…Our study also agreed with Wang, Kuang, and Zhao et al These researchers reported a high diagnostic value of tRFs in early breast cancer, lung cancer, and prostate cancer. 26–28 We also found that the extracellular vesicles-derived tRF-1:30-Lys-CTT-1-M2 was significantly upregulated in the metastatic hypopharyngeal cancer patients as compared with the non-lung metastatic patients. That means tRF-1:30-Lys-CTT-1-M2 was able to differentiate between lung metastatic and non-lung metastatic hypopharyngeal cancer.…”

Section: Discussionmentioning

confidence: 53%

Expression and Diagnostic Value of tRNA-Derived Fragments Secreted by Extracellular Vesicles in Hypopharyngeal Carcinoma

Zeng

et al. 2021

OTT

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To detect the expression level of tRNA-derived fragments secreted by extracellular vesicles in hypopharyngeal cancer and explore the influence of tRNA-derived fragments on the occurrence of hypopharyngeal cancer and lung metastasis. Methods: After high-speed centrifugation, tRNA, which was extracted from the extracellular vesicles of patients with hypopharyngeal cancer and healthy subjects, was sequenced using microarrays. The expression of three differentially expressed tRNAs in hypopharyngeal cancer, healthy subjects, human normal laryngeal epithelial cells and hypopharyngeal cancer line was detected by qRT-PCR. The correlation between the upregulated tRNA, as identified by qRT-PCR, and the clinicopathological features of the non-lung metastatic patients was further analyzed. Finally, the expressions of upregulated tRNA were compared between the non-lung metastatic and lung metastatic patients. The risk factors of hypopharyngeal cancer with lung metastatic were identified by the Cox regression analysis. Results: By high-speed centrifugation, extracellular vesicles were extracted successfully. It was found that a variety of tRNAs in the extracellular vesicles from patients with hypopharyngeal cancer by sequencing. qRT-PCR validation indicated that tRF-1:30-Lys-CTT-1-M2 was significantly overexpressed in hypopharyngeal cancer patients and tumor cells, especially in lung metastatic patients. It was indicated that tRF-1:30-Lys-CTT-1-M2 overexpression was closely related to such pathological features as tumor staging, differentiation grade, smoking history and drinking history. According to the Cox regression analysis, stage III-IV, smoking history, drinking history and tRF-1:30-Lys-CTT-1-M2 overexpression were independent risk factors for metastasis of hypopharyngeal cancer. Conclusion: tRF-1:30-Lys-CTT-1-M2 was overexpressed in patients with hypopharyngeal cancer and was identified as an independent risk factor for lung metastasis. It can be used as a novel biomarker for the diagnosis and lung metastasis monitoring of hypopharyngeal cancer.

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“…In this regard, there is a growing body of evidence linking tRFs with the post-transcriptional regulation of gene expression and RNA processing, as well as with the onset and progression of human malignancies, highlighting their value to be targeted either for the elucidation of disease driver events or the development of modern diagnostics and therapeutics [55]. Finally, the presence of tRFs in the bloodstream, that has been reported previously [29,[56][57][58] and confirmed by our present analysis, clearly supports future studies for exploring their clinical utility as non-invasive cancer markers.…”

Section: Discussionmentioning

confidence: 88%

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

Papadimitriou

Avgeris

Levis

et al. 2020

Cancers

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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.

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Plasma tRNA Fragments Derived from 5′ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer

Cited by 47 publications

References 48 publications

Toward an Understanding of Extracellular tRNA Biology

Toward an Understanding of Extracellular tRNA Biology

Expression and Diagnostic Value of tRNA-Derived Fragments Secreted by Extracellular Vesicles in Hypopharyngeal Carcinoma

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

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