Transfer RNA-derived fragment tRF-28-P4R8YP9LOND5 as a novel serum biomarker for gastric cancer: diagnostic efficacy and clinicopathological correlations.

BACKGROUND: The early diagnostic rate of gastric cancer (GC) is relatively low. Transfer RNA-derived fragments (tRFs), as a class of non-coding RNAs with tumor-specific expression and stability in body fluids, have emerged as highly promising diagnostic candidate biomarkers. However, their application value in GC still requires systematic validation. Therefore, this study aims to systematically evaluate the value of specific tsRNA molecules as novel diagnostic biomarkers for GC by identifying and validating them.

METHODS: After identifying differentially expressed tsRNAs through the OncotRF database, the expression levels of tRF-28-P4R8YP9LOND5 were measured in serum samples from 117 GC patients, 89 healthy controls, and 51 gastritis patients using reverse transcription quantitative polymerase chain reaction (RT-qPCR) technology. The study evaluated the correlation between this biomarker and clinicopathological features, and the diagnostic efficacy of the single biomarker as well as its combination with carcinoembryonic antigen (CEA), cancer antigen 199 (CA199), and CA724 was analyzed using receiver operating characteristic (ROC) curves. Bioinformatics methods were employed to predict potential target genes and enriched signaling pathways.

RESULTS: tRF-28-P4R8YP9LOND5, a 5' tRNA-derived fragment originating from tRNA-Gly-GCC, was significantly upregulated in GC sera (P<0.001), with expression levels positively correlated with tumor invasion depth (T3-T4 stage), advanced tumor, node, and metastasis staging (III-IV), and neurovascular invasion (all P<0.05). The single-biomarker ROC analysis yielded an area under the curve (AUC) of 0.737, while combination with CEA and CA199 improved AUC to 0.821 (GC vs. healthy controls) and 0.883 (GC vs. gastritis patients), with optimal sensitivity of 80.3%. Bioinformatics revealed that several target genes were enriched in key pathways, such as cancer pathways and p53 signaling, which are critical to GC progression. Specifically, genes involved in cell migration, such as claudin-1, and p53 signaling-related genes like TP53 and MDM2, are known to play pivotal roles in GC pathogenesis. These genes have been implicated in the regulation of tumor invasion, metastasis, and response to DNA damage, which are central to the malignant behavior of GC cells.

CONCLUSIONS: This study reveals that tRF-28-P4R8YP9LOND5 has the potential to serve as a novel serum diagnostic marker for GC. It demonstrates significant promise in distinguishing GC from benign conditions such as gastritis and provides a new strategy for early detection. Further studies are needed to explore its biological functions and its potential for therapeutic applications.