Development of a two-circular RNA panel as potential prognostic biomarker for gastric cancer

Background: Circular RNAs (circRNAs) have attracted increasing attention in recent years for their potential application as disease biomarkers due to their high abundance and stability. In this study, we attempted to screen circRNAs that can be used to predict postoperative recurrence and survival in patients with gastric cancer (GC). Methods: High-throughput RNA sequencing was used to identify differentially expressed circRNAs in GC patients with different prognoses. The expression level of circRNAs in the training set (n=136) and validation set (n=167) was detected by quantitative real-time PCR (qRT-PCR). Kaplan–Meier estimator, receiver operating characteristic (ROC) curve and cox regression analysis were used to evaluate the prognostic value of circRNAs on recurrence-free survival (RFS) and overall survival (OS) in GC patients. CeRNA network prediction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the circRNAs with prognostic significance. Results: A total of 259 differentially expressed circRNAs were identified in GC patients with different RFS. We found two circRNAs (hsa_circ_0005092 and hsa_circ_0002647) that highly expressed in GC patients with good prognoses, and subsequently established a predictive model for postoperative recurrence and prognosis evaluation, named circPanel. Patients with circPanellow might have shorter recurrence-free survival (RFS) and overall survival (OS). We also performed circRNA-miRNA-mRNA network prediction and functional analysis for hsa_circ_0005092 and hsa_circ_0002647. Conclusions: CircPanel has the potential to be a prognostic biomarker in GC patients with greater accuracy than a single circRNA and certain traditional tumor markers (e.g., CEA, CA19-9 and CA724). CircRNA expression profile of gastric cancer patients with different prognosis

研究背景：环状RNA（Circular RNAs, circRNAs）因具备高丰度与稳定性，作为疾病生物标志物的潜在应用价值近年来日益受到关注。本研究旨在筛选可用于预测胃癌（gastric cancer, GC）患者术后复发与生存情况的环状RNA。研究方法：采用高通量RNA测序技术，筛选预后不同的胃癌患者体内的差异表达环状RNA。通过实时定量聚合酶链反应（quantitative real-time PCR, qRT-PCR）检测训练集（n=136）与验证集（n=167）中环状RNA的表达水平。采用Kaplan-Meier法、受试者工作特征（receiver operating characteristic, ROC）曲线及Cox回归分析，评估环状RNA对胃癌患者无复发生存期（recurrence-free survival, RFS）与总生存期（overall survival, OS）的预后价值。对具备预后意义的环状RNA开展内源竞争RNA（CeRNA）网络预测、基因本体论（gene ontology, GO）及京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析。研究结果：在无复发生存期存在差异的胃癌患者中，共鉴定出259个差异表达环状RNA。本研究发现两个在预后良好的胃癌患者中高表达的环状RNA（hsa_circ_0005092与hsa_circ_0002647），并据此构建了用于术后复发预测与预后评估的预测模型circPanel。circPanel低表达的患者无复发生存期与总生存期更短。本研究同时针对hsa_circ_0005092与hsa_circ_0002647开展了circRNA-miRNA-mRNA网络预测及功能分析。研究结论：circPanel有望成为胃癌患者的预后生物标志物，其预测准确性优于单个环状RNA及部分传统肿瘤标志物（如癌胚抗原CEA、糖类抗原CA19-9及CA724）。不同预后胃癌患者的环状RNA表达谱