5'-tRNA-halves are dysregulated in clear cell renal cell carcinoma.

PURPOSE: tRNA fragments are dysregulated in various malignancies. Our study was designed to determine the expression of four 5'-tRNA-halves in tissue and serum of clear cell renal cell carcinoma (ccRCC) patients.

MATERIALS AND METHODS: Tissue and serum samples of patients with ccRCC and non-malignant disease were collected prospectively in our Biobank. We isolated total RNA from 95 ccRCC and 50 normal renal tissues as well as serum RNA from 27 patients with ccRCC and 13 with non-malignant urological diseases. In order to determine specifically the expression of 5'-tRNA halves, we dephosphorylated and ligated an adaptor nucleotide to the 3'-end of the tRNA halves. The expression levels of four 5'-tRNA-halves (5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC, 5'-tRNA-Leu-CAG, 5'-tRNA-Lys-TTT) were then measured by TaqMan-based qRT-PCR.

RESULTS: All studied 5'-tRNA-halves were downregulated in ccRCC tissues indicating a potential role as tumor suppressor. Furthermore, we noticed a decreased expression of 5'-tRNA-halves in patients with adverse clinicopathological parameters: All 5'-tRNA-halves were expressed at lower levels in in non-organ confined ccRCC and 5'-tRNA-Lys-TTT halves were inversely correlated with ISUP Grade. 5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC and 5'-tRNA-Lys-TTT halves were circulating at lower levels in ccRCC patients compared to control subjects indicating its relevance as non-invasive biomarker.

CONCLUSIONS: 5'-tRNA halves have the potential as diagnostic and prognostic biomarker for patients with ccRCC. The 5'-tRNA-halves may act in a tumor suppressive manner which requires further research to confirm.