Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 as novel diagnostic biomarkers for lung adenocarcinoma

Abstract

ObjectiveTRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are recognized as novel and potential types of non-coding RNAs (ncRNAs), and several tRF/tiRNA signatures are closely associated with tumor diagnosis. This study aimed to analyze the expression profiles of plasma tRFs/tiRNAs and to clarify their diagnostic value in lung adenocarcinoma (LUAD).MethodsThe differential expression profiles of plasma tRFs/tiRNAs in patients with four patients with early LUAD, four patients with advanced LUAD, and four healthy controls were analyzed using high-throughput sequencing technology. Then, plasma tRFs/tiRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR), and their diagnostic efficiency was appraised by receiver operating characteristic curve analysis. The correlation of candidate plasma tRFs/tiRNAs with clinicopathological features was also analyzed. Finally, bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs/tiRNAs.ResultsThe sequencing results revealed that tRFs/tiRNAs from plasma samples in patients with LUAD were differently expressed, supporting the necessity of exploring their potential as biomarkers. The validation results of qRT-PCR demonstrated that the expression level of tRF-1:29-Pro-AGG-1-M6 was downregulated in LUAD, while that of tRF-55:76-Tyr-GTA-1-M2 was upregulated, which was consistent with the sequencing data. The areas under the receiver operating characteristic curve of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 were 0.882 and 0.896, respectively, which have significant values in the diagnosis of LUAD. The expressions of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 in LUAD were obviously correlated with various clinicopathological features such as tumor–node–metastasis stage, node stage, and the expression levels of carcinoembryonic antigen. In addition, their expression was significantly altered from before to after tumor resection in LUAD patients. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses further indicated that tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 are widely distributed and apparently enriched in several tumor-related signaling pathways.ConclusionsPlasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 may be promising components in the development of highly sensitive and non-invasive biomarkers for LUAD diagnosis.

In lung adenocarcinoma, low expression of the cell surface extracellular nucleotidase CD39 is related to immune infiltration and a poor prognosis

“…Since lung adenocarcinoma is one of the most prevalent cancer types and one of the malignant tumors with the maximum mortality and morbidity, understanding the molecular mechanism of CD39 may assist in the discovery of clinically effective therapies or exploration of compelling predictive biomarkers ( 21 ). Many studies have shown that CD39 is crucial to the development and progression of many cancers and diseases ( 22 , 23 ).…”

tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application

“…Recent investigations have demonstrated promising levels of sensitivity and specificity of tsRNAs observed in tumor tissues and body fluids. The abnormal expression patterns of tsRNAs identified in patients with tumors highlight their potential to act as a new biomarker for tumor diagnosis [ 166 – 173 ] (table 3 ). In their study, you et al [ 166 ] identified a downregulation in tRF-1:29-Pro-AGG-1-M6 expression in the plasma of patients with LUAD via tRF/tiRNA sequencing.…”

“…The abnormal expression patterns of tsRNAs identified in patients with tumors highlight their potential to act as a new biomarker for tumor diagnosis [ 166 – 173 ] (table 3 ). In their study, you et al [ 166 ] identified a downregulation in tRF-1:29-Pro-AGG-1-M6 expression in the plasma of patients with LUAD via tRF/tiRNA sequencing. In contrast, an upregulation in tRF-55:76-Tyr-GTA-1-M2 expression was also observed, which was consistent with qRT-PCR results.…”