RESUMEN
Objective: TRNA-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). Methods: The 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. Results: The 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. Conclusions: Plasma 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.
RESUMEN
Background: Lung cancer (LC) is ranked as a leading cause of cancer-related death worldwide. However, there are still few reliable screening biomarkers for daily clinical practice in LC. Circular RNAs (circRNAs) have been suggested as valuable diagnostic biomarkers in various cancers. In this study, the expression and diagnostic potential of several circRNAs for LC were explored. Methods: Seventy-two pairs of LC tissues and adjacent normal lung tissues were collected to measure the relative expression level of circRNAs using quantitative reverse transcription-polymerase chain reaction. In addition, the relationships between circRNAs and the clinicopathological features of LC patients were analyzed. Furthermore, the sensitivities and specificities of the circRNAs were evaluated by receiver operating characteristic (ROC) analysis. Results: The expression levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, has_circ_0074368, and has_circ_0000896 were downregulated in LC tissues compared with adjacent normal lung tissues. The lower levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, and has_circ_0000896 were significantly correlated with advanced disease stages. The area under the ROC curves of has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 were 0.833, 0.793, 0.773, 0.730, and 0.645, respectively. Conclusions: Has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 are capable of distinguishing LC tissues from normal lung tissues. Besides, the biggest area under the ROC curve value of has_circ_000249 suggests it appears to be a better diagnosis marker for LC patients.
