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

Jianbin You; Guoliu Yang; Yi Wu; Xuan Lu; Shuyu Huang; Qianshun Chen; Chen Huang; Falin Chen; Xunyu Xu; Liangyuan Chen

doi:10.3389/fonc.2022.991451

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

Front Oncol. 2022 Sep 20:12:991451. doi: 10.3389/fonc.2022.991451. eCollection 2022.

Authors

Jianbin You¹, Guoliu Yang¹, Yi Wu², Xuan Lu³, Shuyu Huang⁴, Qianshun Chen⁵, Chen Huang⁵, Falin Chen¹, Xunyu Xu⁵, Liangyuan Chen¹

Affiliations

¹ Department of Clinical Laboratory, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
² Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.
³ Department of Clinical Laboratory, Zhangzhou Skin Disease Prevention and Treatment Hospital of Fujian Province, Zhangzhou, China.
⁴ Department of Blood Transfusion, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
⁵ Department of Thoracic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.

Abstract

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.

Keywords: biomarkers; high-throughput sequencing; lung adenocarcinoma; plasma; tRFs/tiRNAs.