Absolute quantification of a plasma tRNA-derived fragment for the diagnosis and prognosis of gastric cancer

BACKGROUND: The transition from a healthy gastric mucosa to gastric cancer is a multi-step process. Early screening can significantly improve the survival rate of gastric cancer patients. A reliable liquid biopsy for gastric cancer prediction is urgently needed and since tRNA-derived fragments (tRFs) are abundant in various body fluids, tRFs are possible new biomarkers for gastric cancer. METHODS: A total of 438 plasma samples from patients with different gastric mucosal lesions as well as healthy individuals were collected. A specific reverse transcription primer, a forward primer, a reverse primer, and a TaqMan probe were designed. A standard curve was constructed and an absolute quantitation method was devised for detection of tRF-33-P4R8YP9LON4VDP in plasma samples of individuals with differing gastric mucosa lesions. Receiver operating characteristic curves were constructed to evaluate the diagnostic values of tRF-33-P4R8YP9LON4VDP for individual with differing gastric mucosa. A Kaplan–Meier curve was established to calculate the prognostic value of tRF-33-P4R8YP9LON4VDP for advanced gastric cancer patients. Finally, a multivariate Cox regression analysis was performed to assess the independent prognostic value of tRF-33-P4R8YP9LON4VDP for advanced gastric cancer patients. RESULTS: A detection method for plasma tRF-33-P4R8YP9LON4VDP was successfully established. Levels of plasma tRF-33-P4R8YP9LON4VDP were shown to reflect a gradient change from healthy individuals to gastritis patients to early and advanced gastric cancer patients. Significant differences were found among individuals with differing gastric mucosa, with reduced levels of tRF-33-P4R8YP9LON4VDP significantly related to a poor prognosis. tRF-33-P4R8YP9LON4VDP was found to be an independent predictor of an unfavorable survival outcome. CONCLUSIONS: In this study, we developed a quantitative detection method for plasma tRF-33-P4R8YP9LON4VDP that exhibited hypersensitivity, convenience, and specificity. Detection of tRF-33-P4R8YP9LON4VDP was found to be a valuable means by which to monitor different gastric mucosa and to predict patient prognosis.