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

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).

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.

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).

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.