血清外泌体hsa_circ_0008035在胃癌前病变和早期胃癌中的临床意义

Clinical value of serum exosome hsa_circ_0008035 in premalignant gastric lesions and early gastric cancer

目的 探讨血清外泌体hsa_circ_0008035在早期胃癌(GC)及癌前病变中的临床意义。方法 2012年1月~2017年12月于我院就诊的GC病人90例(GC组)、癌前病变病人外周血样本89例(Pre组),同期纳入45例健康志愿者外周血样本作为对照(NC组),实时荧光定量聚合酶链式反应(qRT-PCR)检测血清外泌体hsa_circ_0008035水平。绘制受试者工作特征(ROC)曲线评估血清外泌体hsa_circ_0008035的诊断价值。通过内镜检查随访Pre组病人疾病进展情况。基于circBase和RegRNA 2.0靶点预测软件获得hsa_circ_0008035潜在的microRNA(miRNA)靶点。结果 与NC组比较,GC组和Pre组病人血清外泌体hsa_circ_0008035表达水平显著上调,其中GC组升高最为明显(P<0.05)。与传统肿瘤标志物检测比较,外泌体hsa_circ_0008035诊断GC及Pre的曲线下面积(AUC)、敏感性、准确性均显著提高,假阴性率和假阳性率显著降低(P<0.05)。在区分早期GC和Pre病人时的AUC为0.681,灵敏度和特异度为66.35%和83.31%。Pre组病人中位随访5.3年,21例病人发生疾病进展,这部分病人诊断为疾病进展时血清外泌体hsa_circ_0008035表达水平较基线值显著上调(P<0.001),基线时血清外泌体hsa_circ_0008035表达水平也较未发生疾病进展的病人普遍上调(P=0.005)。对于GC组病人,中晚期GC(TNM分期Ⅲ~Ⅳ期)病人血清外泌体hsa_circ_0008035表达水平高于早期GC病人,差异有统计学意义(P<0.05)。hsa_circ_0008035靶通路预测结果显示,hsa_circ_0008035含有hsa-miR-599、hsa-miR-17-3p、hsa-miR-1256和hsa-miR-375种子序列及相关的常见下游靶点。结论 血清外泌体hsa_circ_0008035表达在早期GC及癌前病变病人中普遍上调,对早期GC、胃癌前病变的诊断和疾病进展的评估均有一定的临床意义。

Objective To investigate the clinical value of serum exosome hsa_circ_0008035 in early gastric cancer(GC)and premalignant gastric lesions(Pre).Methods The peripheral blood samples of 90 GC patients(GC group)and 89 premalignant gastric lesions(Pre group)who visited our hospital from January 2012 to December 2017 were collected.At the same time,45 healthy volunteers were included as the control group(NC group).And quantitative real-time fluorescence polymerase chain reaction(qRT-PCR)was used to detect serum exosomal hsa_circ_0008035 Horizontal.Receiver operating characteristic(ROC)curve was drew to evaluate serum exosomal hsa_circ_0008035.Follow up the disease progression of Pre group patients through endoscopic examination.Finally,Based on circBase and RegRNA 2.0 target prediction software to seek the potential microRNA(miRNA)targets of hsa_circ_0008035.Results Compared with NC group,the expression level of serum exosomal hsa_circ_0008035 in GC group or Pre group were significantly increased,with the most pronounced increase in the GC group(P<0.05).Compared with traditional tumor markers detection,the area under curve(AUC),sensitivity and accuracy of exosomal hsa_circ_0008035 in the diagnosis of GC and Pre were significantly increased,and the false negative rate and false positive rate were significantly decreased(P<0.05).The AUC was 0.681,a sensitivity and specificity were 66.35%and 83.31%of exosomal hsa_circ_0008035 in distinguishing between patients with early GC and Pre.For the Pre group patients,a median follow-up of 5.3 years was observed,during which 21 patients experienced disease progression.These patients were diagnosed with a significant increase in serum exosome hsa_circ_0008035 expression level compared to baseline(P<0.001).Moreover,the serum exosome hsa_circ_0008035 expression level at baseline was generally higher than that of patients without disease progression(P=0.005).For patients in the GC group,the expression level of serum exosomal hsa_circ_0008035 in patients with middle and advanced GC(TNM stageⅢ-Ⅳ)was higher than that in patients with early GC(P<0.05).Hsa_circ_0008035 target pathway prediction results showed that hsa_circ_0008035 contained hsa-miR-599,hsa-miR-17-3p,hsa-miR-1256 and hsa-miR-375 seed sequences and related common downstream targets.Conclusion The expression of serum exosomal hsa_circ_0008035 is generally increased in the patients with early GC and premalignant gastric lesions,which has has certain clinical significance for the diagnosis of early GC and premalignant gastric lesions,and evaluation of disease progression.