Abstract
Gastric cancer (GC) presents with insidious early symptoms that lack distinctiveness. Coupled with insufficient screening awareness and limited diagnostic methods, these symptoms are difficult to distinguish from manifestations of benign conditions including gastritis and gastric ulcers, leading patients to seek medical attention only after advanced-stage symptoms develop. Traditional serum markers exhibit low positivity and specificity in early-stage GC; therefore, actively identifying novel molecules for combined diagnosis in conjunction with traditional biomarkers proves essential for the early diagnosis of GC. tRNA-derived small RNAs (tsRNAs), a novel category of non-coding RNAs (ncRNAs), exhibit promise as liquid biopsy indicators and can engage in the pathological processes of cancer through diverse molecular pathways. In this study, we seek to identify tsRNAs that may facilitate the diagnosis and prognostic surveillance of GC, thus offering a substantial scientific foundation for enhancing the precision diagnosis and therapy of GC, as well as clarifying its pathological mechanisms.In this study, microarray detection technology was employed to analyze serum samples from 5 patients with stage ⅠGC, 5 with stage II-III GC, 5 with superficial gastritis, and 5 healthy donors. Subsequently, tsRNAs with significantly upregulated expression in GC serum were identified by comparative analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen tRF-18-HR05X6D2 as a target for further analysis in tissues, serum, and cells. The stability of tRF-18-HR05X6D2 detection performance was evaluated through room-temperature incubation and repeated freeze-thaw cycle experiments. tRF-18-HR05X6D2 was identified and analyzed via agarose gel electrophoresis (AGE), Sanger sequencing, and RNA isolation methods. qRT-PCR was applied to determine the differential expression levels of tRF-18-HR05X6D2 in serum from a large cohort of clinical specimens. The correlation between tRF-18-HR05X6D2 expression levels and clinicopathological parameters was assessed via chi-square test, complemented by the construction of receiver operating characteristic (ROC) curves, on the other hand, was employed to evaluate its diagnostic performance. We predict its downstream target genes by bioinformatics analysis. Finally, we explored its function in cells through in vitro experiments.The expression of tRF-18-HR05X6D2 was found to be elevated in the serum of GC patients, as well as in GC tissues and GC cell lines. Serum levels of tRF-18-HR05X6D2 were associated with tumor dimensions, invasive depth, lymph node involvement, TNM classification, and vascular infiltration. Following surgical treatment, tRF-18-HR05X6D2 expression was decreased. The combination of tRF-18-HR05X6D2 with carcinoembryonic antigen (CEA), carbohydrate antigen 72-4 (CA72-4), and carbohydrate antigen 19-9 (CA19-9) can significantly improve the diagnostic efficacy of GC. Cell function experiments suggested that tRF-18-HR05X6D2 could promote the proliferation, migration, and invasion of GC cells. Based on the aforementioned results, tRF-18-HR05X6D2 shows promise as a diagnostic indicator for GC.tRF-18-HR05X6D2 exhibits promise not just as a non-invasive marker for the early diagnosis of GC, but also as a predictor of disease progression.