Plasma exosomal tRNA-derived fragments as diagnostic biomarkers in non-small cell lung cancer

Baibing Zheng; Xingguo Song; Li Wang; Yue Zhang; Youyong Tang; Shiwen Wang; Lei Li; Yawen Wu; Xianrang Song; Li Xie

doi:10.3389/fonc.2022.1037523

Plasma exosomal tRNA-derived fragments as diagnostic biomarkers in non-small cell lung cancer

Front Oncol. 2022 Oct 31:12:1037523. doi: 10.3389/fonc.2022.1037523. eCollection 2022.

Authors

Baibing Zheng¹, Xingguo Song¹, Li Wang¹, Yue Zhang¹, Youyong Tang¹, Shiwen Wang¹, Lei Li², Yawen Wu¹, Xianrang Song^{1

3}, Li Xie¹

Affiliations

¹ Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
² School of Medical Laboratory, Weifang Medical University, Weifang, China.
³ Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Abstract

Background: tRNA derived small RNAs (tRFs) have recently received extensive attention; however, the effects of tRFs in exosome as biomarkers has been less studied. The objective of this study was to validate novel diagnostic exosomal tRFs with sensitivity and specificity for non-small cell lung cancer (NSCLC).

Methods: Exosomes extracted from plasma of NSCLC patients and healthy individuals were identified by transmission electron microscopy (TEM), qNano and western blots. The differentially expressed tRFs were screened by high-throughput sequencing in plasma exosomes of NSCLC patients and healthy individuals, and further verified by Quantitative Real-Time PCR (qRT-PCR). To assess the diagnostic efficacy of exosomal tRFs for NSCLC, receiver operating characteristic (ROC) curves were used next.

Results: The expression levels of exosomal tRF-Leu-TAA-005, tRF-Asn-GTT-010, tRF-Ala-AGC-036, tRF-Lys-CTT-049, and tRF-Trp-CCA-057 were significantly decreased in NSCLC patients and early-stage NSCLC patients compared to healthy individuals. Notably, the exepression of tRF-Leu-TAA-005, tRF-Asn-GTT-010, tRF-Ala-AGC-036, tRF-Lys-CTT-049, and tRF-Trp-CCA-057 in the exosomes were higher than the exosome depleted supernatant (EDS).

Conclusions: Our results showed that the levels of exosomal tRF-Leu-TAA-005, tRF-Asn-GTT-010, tRF-Ala-AGC-036, tRF-Lys-CTT-049, and tRF-Trp-CCA-057 were significantly downregulated in NSCLC patients. This suggests that these five exosomal tRFs may be promising diagnostic biomarkers for NSCLC.

Keywords: NSCLC; biomarker; diagnosis; exosomal tRFs; plasma.