Elucidating the Role of Serum tRF-31-U5YKFN8DYDZDD as a Novel Diagnostic Biomarker in Gastric Cancer (GC).

Yuejiao Huang,Chunlei Peng,Shaoqing Ju,Xinliang Gu,Xiangrong Shi,Shiyi Qin,Haiyan Zhang,Ming Zheng

doi:10.3389/fonc.2021.723753

Abstract

BackgroundGastric cancer (GC) is one of the malignant tumors with the highest morbidity and mortality in the world. Early diagnosis combined with surgical treatment can significantly improve the prognosis of patients. Therefore, it is urgent to seek higher sensitivity and specificity biomarkers in GC. tRNA-derived small RNAs are a new non-coding small RNA that widely exists in tumor cells and body fluids. In this study, we explore the expression and biological significance of tRNA-derived small RNAs in GC.Materials and MethodsFirst of all, we screened the differentially expressed tRNA-derived small RNAs in tumor tissues by high-throughput sequencing. Agarose gel electrophoresis (AGE), Sanger sequencing, and Nuclear and Cytoplasmic RNA Separation Assay were used to screen tRF-31-U5YKFN8DYDZDD as a potential tumor biomarker for the diagnosis of GC. Then, we detected the different expressions of tRF-31-U5YKFN8DYDZDD in 24 pairs of GC and paracancerous tissues, the serum of 111 GC patients at first diagnosis, 89 normal subjects, 48 superficial gastritis patients, and 28 postoperative GC patients by quantitative real-time PCR (qRT-PCR). Finally, we used the receiver operating characteristic (ROC) curve to analyze its diagnostic efficacy.ResultsThe expression of tRF-31-U5YKFN8DYDZDD has good stability and easy detection. tRF-31-U5YKFN8DYDZDD was highly expressed in tumor tissue, serum, and cell lines of GC, and the expression was significantly related to TNM stage, depth of tumor invasion, lymph node metastasis, and vascular invasion. The expression of serum tRF-31-U5YKFN8DYDZDD in the GC patients decreased after the operation (P = 0.0003). Combined with ROC curve analysis, tRF-31-U5YKFN8DYDZDD has better detection efficiency than conventional markers.ConclusionsThe expressions of tRF-31-U5YKFN8DYDZDD in the tumor and paracancerous tissues, the serum of GC patients and healthy people, and the serum of GC patients before and after operation were different. tRF-31-U5YKFN8DYDZDD is not only a diagnostic biomarker of GC but also a predictor of poor prognosis.

Highlights

There are nearly one million new cases of gastric cancer (GC) in the world every year, and China accounts for about 40% of all, with the morbidity and mortality ranking among the top three malignancies in China [1, 2]
The expression of Transfer RNA (tRNA)-derived fragments (tRFs)-31-U5YKFN8DYDZDD has good stability and easy detection. tRF-31-U5YKFN8DYDZDD was highly expressed in tumor tissue, serum, and cell lines of GC, and the expression was significantly related to TNM stage, depth of tumor invasion, lymph node metastasis, and vascular invasion
Yu et al demonstrated that the sensitivity of CEA in the diagnosis of gastric cancer is about 13–35%, while the specificity is only about 65%, and the carbohydrate antigen 199 (CA199) is about 40 and 70%, Abbreviations: GC, Gastric cancer; AGE, Agarose gel electrophoresis; qRT-PCR, quantitative real-time PCR; receiver operating characteristic (ROC), Receiver operating characteristic; CEA, Carcinoembryonic antigen; CA199, Carbohydrate antigen 199; carbohydrate antigen 724 (CA724), Carbohydrate antigen 724; ncRNAs, non-coding RNA; tRNAs, transfer RNA; tsRNAs, tRNA-derived small RNAs; tRFs, tRNA-derived fragments; tiRNAs, tRNA halves; U6, RNU6B; area under the curve (AUC), Area under the curve; confidence interval (CI), Confidence interval; standard deviation (SD), Standard deviation; coefficient of variation (CV), Coefficient of variation; SEN, Sensitivity; SPE, Specificity; ACCU, Overall accuracy; positive predictive value (PPV), Positive predictive value; negative predictive value (NPV), Negative predictive value; EMT, epithelial to mesenchymal transformation; Runx 1, runt-related transcription factor 1

Summary

Introduction

There are nearly one million new cases of gastric cancer (GC) in the world every year, and China accounts for about 40% of all, with the morbidity and mortality ranking among the top three malignancies in China [1, 2]. GC is derived from the malignant transformation of gastric epithelial cells, and its pathological type is mainly adenocarcinoma [3]. Because it is a hollow organ, the clinical symptoms in the early stage of malignant transformation are not obvious, mainly nausea, which is difficult to distinguish from diseases such as gastritis. It is of great clinical significance to improve the prognosis of patients with GC by early diagnosis and treatments [4]. Carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) are relatively mature tumor biomarkers in clinical use at present, but their specificity and sensitivity are not high [6]. We explore the expression and biological significance of tRNA-derived small RNAs in GC

Methods

Results

Discussion

Conclusion