Xu Yanhua, Kong Shan, Qin Xinyue, Ju Shaoqing
Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, People's Republic of China.
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, People's Republic of China.
Onco Targets Ther. 2020 Oct 8;13:10063-10074. doi: 10.2147/OTT.S263536. eCollection 2020.
Due to the lack of specific and sensitive detection indicators, most patients with GC are already in the advanced stage at the time of diagnosis. Therefore, it is urgent to search for effective diagnostic biomarkers that can be applied in clinic.
We screened out circ_0004771 through circRNA sequencing. Exonuclease digestion assay, agarose gel electrophoresis (AGE) and Sanger sequencing verified the potential of circ_0004771 being a biomarker. Additionally, we established quantitative real-time fluorescent polymerase chain reaction (qRT-PCR) to detect the expression level of circ_0004771 and evaluated the methodology. What's more, we collected plasma samples from 120 GC patients, 40 superficial gastritis patients, 20 postoperative GC patients, 20 postoperative recurrence patients and 120 healthy donors. We constructed the receiver operating characteristic curve (ROC) to appraise its diagnostic efficacy.
The expression level of circ_0004771 is up-regulated in GC tissues, which is consistent with circRNA sequencing result (P=0.0001). Circ_0004771 can serve as a promising biomarker because of its stable structure and longer half-life. Plasma circ_0004771 expression is markedly richer in GC patients than that in normal people (P<0.0001), and the area under the ROC (AUC) is 0.831 (95% CI: 0.779-0.883). The diagnostic efficacy of circ_0004771 is higher than that of CEA (AUC=0.747, 95% CI: 0.686-0.808) and CA199 (AUC=0.508, 95% CI: 0.433-0.583). Higher diagnostic efficacy can be achieved by combination diagnosis for distinguishing GC patients from normal people (AUC=0.864). Besides, the expression level of circ_0004771 can distinguish GC patients from gastritis patients (AUC=0.845, 95% CI: 0.772-0.917). The plasma circ_0004771 expression in GC patients decreased to normal after surgery (P<0.0001). In addition, plasma circ_0004771 expression increased again in patients with postoperative recurrence.
Plasma circ_0004771 is differentially expressed in GC patients, postoperative GC patients and patients with recurrence, suggesting that plasma circ_0004771 can be used as a novel diagnostic and dynamic monitoring biomarker in GC.
由于缺乏特异性和敏感性高的检测指标，大多数胃癌患者在确诊时已处于晚期。因此，迫切需要寻找可应用于临床的有效诊断生物标志物。
我们通过环状RNA测序筛选出circ_0004771。核酸外切酶消化试验、琼脂糖凝胶电泳（AGE）和桑格测序验证了circ_0004771作为生物标志物的潜力。此外，我们建立了定量实时荧光聚合酶链反应（qRT-PCR）来检测circ_0004771的表达水平并评估该方法。而且，我们收集了120例胃癌患者、40例浅表性胃炎患者、20例胃癌术后患者、20例术后复发患者和120例健康供者的血浆样本。我们构建了受试者工作特征曲线（ROC）来评估其诊断效能。
circ_0004771在胃癌组织中的表达水平上调，这与环状RNA测序结果一致（P = 0.0001）。由于其结构稳定且半衰期较长，circ_0004771可作为一种有前景的生物标志物。胃癌患者血浆中circ_0004771的表达明显高于正常人（P < 0.0001），ROC曲线下面积（AUC）为0.831（95%CI：0.779 - 0.883）。circ_0004771的诊断效能高于癌胚抗原（CEA，AUC = 0.747，95%CI：0.686 - 0.808）和糖类抗原199（CA199，AUC = 0.508，95%CI：0.433 - 0.583）。联合诊断区分胃癌患者和正常人可获得更高的诊断效能（AUC = 0.864）。此外，circ_0004771的表达水平可区分胃癌患者和胃炎患者（AUC = 0.845，95%CI：0.772 - 0.917）。胃癌患者术后血浆circ_0004771表达降至正常水平（P < 0.0001）。此外，术后复发患者血浆circ_0004771表达再次升高。
血浆circ_0004771在胃癌患者、胃癌术后患者和复发患者中存在差异表达，提示血浆circ_0004771可作为胃癌新型诊断及动态监测的生物标志物。
