tRNA-derived fragments in gastric cancer: Biomarkers and functions

Abstract

tRNA-derived fragments (tRFs), non-coding RNAs that regulate protein expression after transcription, have recently been identified as potential biomarkers. We identified differentially expressed tRFs in gastric cancer (GC) and the biological properties of tRFs in predicting the malignancy status of GCs as possible biomarkers. Until 15 February 2022, two independent reviewers did a thorough search in electronic databases of Scopus, EMBASE and PubMed. The QUADAS scale was used for quality assessment of the included studies. Ten articles investigating the clinical significance of tRFs, including 928 patients, were analysed. In 10 GC studies, seven tRFs were considerably upregulated and five tRFs were significantly downregulated when compared to controls. Risk of bias was rated low for index test, and flow as well as timing domains in relation to the review question. The applicability of the index test, flow and timing and patient selection for 10 studies was deemed low. In this study, we review the advances in the study of tRFs in GC and describe their functions in gene expression regulation, such as suppression of translation, cell differentiation, proliferation and the related signal transduction pathways associated with them. Our findings may offer researchers new ideas for cancer treatment as well as potential biomarkers for further research in GC.

Keywords: Gastric cancer; biomarker; tRNA-derived Fragments.

FIGURE 1

The classification of tRFs. tRF‐1, ‐2, ‐3 tRF‐5 are examples of tRNA‐Derived Fragments (TRFs). tRF‐1 is generated from the 3′‐end of pre‐tRNA. tRF‐2 is a tRNA fragment with an anti‐codon loop generated by an unknown cleavage method. tRF‐5 and tRF‐3 are derived from 5′‐, 3′‐ the ends of mature tRNAs, respectively. i‐tRF is derived from the mature tRNA's internal region.

FIGURE 2

tRFs used as diagnosis biomarkers. We discovered that multiple different tRFs from both the up‐ and down‐regulated tRFs groups were involved in GC. Some tRFs were upregulated and others were downregulated.

FIGURE 3

The study selection process is depicted as a flow diagram. A flow diagram of the study selection process was showed. A total of 38 studies in PubMed/Medline, EMBASE and Scopus was retrieved. All studies were screened according to role of tRFs in GC. A final total of 10 articles, including tRFs studies for comparing the expression of tRFs in GC patients and healthy people were used for the paper review.

FIGURE 4

Methodological quality graph. The comprehensive results of the QUADAS2 quality evaluation were showed. These studies did not provide sensitivity and specificity data.

FIGURE 5

Characteristics of tRFs used as potential biomarkers of GC. The significance and characteristics of multiple tRFs in gastric tumour development and therapeutics.

FIGURE 6

Characteristics required for biomarkers of GC. Biomarkers of GC is minimally or noninvasive, high specificity and sensitivity.