A newly screened mitochondrial tRNA fragment as a serum biomarker for diagnosis of gastric cancer

Gastric cancer (GC) is a common digestive malignancy with high mortality, and current serum-based biomarkers lack sensitivity (SEN) and specificity (SPE) for GC detection. The aim of this study was to assess the diagnostic value of a newly screened mitochondrial tRNA fragment (mt-tRF) tRF-21-EXEY0VWUD as a serum biomarker in GC patients. An mt-tRF molecule, tRF-21-EXEY0VWUD, was screened from the OncotRF database. The relative expression levels of tRF-21-EXEY0VWUD were measured using reverse transcription–quantitative polymerase chain reaction (RT–qPCR) in serum samples from primary GC patients ( n = 122), patients with chronic gastritis ( n = 46), postoperative gastric cancer patients ( n = 48), healthy donors ( n = 101) and 21 paired GC tissues and adjacent normal tissues. Methodological validation was performed for the RT–qPCR assay. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and clinicopathological correlation analysis in SPSS software. Potential biological functions associated with its abnormal expression were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The mt-tRF tRF-21-EXEY0VWUD was significantly upregulated in GC cells, serum, and tissues compared with controls ( P < 0.05), and exhibited high stability and precision when quantified by RT–qPCR. ROC analysis yielded an area under the curve (AUC) of 0.736. This value is higher than those of conventional biomarkers, indicating good diagnostic accuracy. Exploratory clinicopathological analysis revealed that the expression level of tRF-21-EXEY0VWUD was associated with tumor differentiation grade ( P < 0.05), TNM stage ( P < 0.01), and neural/vascular invasion ( P < 0.001) in GC patients. Bioinformatics-based GO and KEGG enrichment analyses predicted potential functional roles in immune modulation, calcium signaling, and mechanistic target of rapamycin (mTOR) pathway regulation. The mt-tRF tRF-21-EXEY0VWUD has considerable potential as a serological marker for the detection of GC. The combined detection of this fragment with classical tumor markers can increase the diagnostic accuracy and support more reliable clinical stratification.