Dysregulated transfer RNA-derived small RNAs as potential gastric cancer biomarkers.

Abstract

Gastric cancer (GC) is the kind of carcinoma that has the highest rates of morbidity and death worldwide. In the early stages of GC, there is currently an absence of sensitive and specific biomarkers. The newly-discovered class of non-coding RNAs (ncRNAs) known as transfer RNA-derived small RNAs (tsRNAs) is highly expressed in bodily fluids and neoplastic cells. High-throughput sequencing was initially employed to identify differentially expressed tsRNAs in early GC patients, followed by validation in patient serum, GC tissues, and cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). We identified dysregulated tsRNAs (the up-regulated tsRNAs included tRF-31-PNR8YP9LON4VD, tRF-30-MIF91SS2P4FI, and tRF-30-IK9NJ4S2I7L7, whereas the down-regulated tsRNAs included tRF-38-W6RM7KYUPRENRHD2, tRF-37-LBRY73W0K5KKOV2, tRF-36-JB59V3WD8YQ84VD, tRF-25-MBQ4NKKQBR, and tRF-36-0KFMNKYUHRF867D) in GC, and we verified that the serum of patients, GC cells and tissues both consistently expressed these tsRNAs. Additionally, GC patients' serum had considerably greater expression levels of the three up-regulated tsRNAs than did healthy controls. Receiver operating characteristic (ROC) curve analysis demonstrated that the sensitivity and specificity of the three up-regulated tsRNAs were superior to those of CEA, CA199, and CA724 in the process of diagnosing GC, particularly in its early stages. This suggests that tsRNAs have great diagnostic efficacy and potential as new "liquid biopsy" biomarkers for the diagnosis of GC. Using bioinformatics software, we predicted that dysregulation of tsRNAs may be a potential regulatory mechanism for the development of GC.