结直肠癌患者血清外泌体circRASGRF2的水平和临床意义

Clinical significance of serum exosomal circRASGRF2 in the diagnosis and prognosis of colorectal cancer patients

目的探讨血清外泌体环状RNA circRASGRF2(hsa_circ_0073181)在结直肠癌(CRC)诊断和预后评估中的临床意义。方法收集本院2017年1月至2019年12月的126例CRC患者和139例体检健康者的外周血标本,制备血清后经试剂盒提取外泌体,实时荧光定量PCR(qPCR)法检测血清外泌体的circRASGRF2水平并采用受试者工作特征(ROC)曲线分析circRASGRF2水平诊断CRC的效能,结合临床病理资料和随访数据分析血清外泌体circRASGRF2的临床意义。结果CRC患者的血清外泌体circRASGRF2水平[中位数(25%~75%四分位数范围)]为4.292(3.045~4.897),高于体检健康者的1.335(1.062~1.692),差异有统计学意义(P<0.05)。ROC分析显示血清外泌体circRASGRF2水平诊断CRC的曲线下面积为0.934(95%CI:0.902~0.966),当最佳截断值为2.227时约登指数最大,灵敏度和特异度分别为86.51%和91.37%。血清外泌体circRASGRF2水平与T分期、N分期、TNM分期、肿瘤大小和血清癌胚抗原基线水平有关(P<0.05),而与年龄、性别、肿瘤部位、分化程度和KRAS外显子2状态无关(P>0.05)。预后分析显示血清外泌体circRASGRF2水平与CRC患者的总生存期(OS)有关,其中低水平组的中位OS未达,1、3、5年生存率分别为100.0%、78.8%和48.1%,优于高水平组的47.0个月及93.7%、51.1%和14.3%(HR=3.438,95%CI:2.097~5.638,P<0.001),进一步多因素分析发现其水平升高是CRC患者预后不良的危险因素(HR=3.065,95%CI:2.745~5.266,P=0.009)。结论CRC患者血清外泌体circRASGRF2水平升高,且与不良预后和恶性进展指标有关,有望成为CRC诊治指导和预后评估的潜在指标。

Objective To investigate the clinical significance of serum exosomal circular RNA circRASGRF2(hsa_circ_0073181)in the diagnosis and prognosis of colorectal cancer(CRC).Methods Peripheral blood samples from 126 patients with CRC and 139 healthy people in our hospital from January 2017 to December 2019 were collected.After serum was prepared,exosomes were extracted by the kit.The level of circRASGRF2 in serum exosomes was detected by real-time fluorescent quantitative PCR(qPCR).The efficacy of circRASGRF2 in diagnosing CRC was analyzed by using the receiver operating characteristic(ROC)curve.The clinical significance of circRASGRF2 in serum exosomes was analyzed by combining clinical pathological data and follow-up data.Results The serum exosomal circRASGRF2 level in CRC patients[median(25%-75%interquartile range)]was 4.292(3.045-4.897),higher than 1.335(1.062-1.692)in healthy subjects(P<0.05).ROC analysis showed that the area under the curve of serum exosomal circRASGRF2 level in diagnosis of CRC was 0.934(95%CI:0.902-0.966).When the optimal cutoff value was 2.227,the yoden index was the largest,and the sensitivity and specificity were 86.51%and 91.37%,respectively.The level of serum exosomal circRASGRF2 was correlated with T stage,N stage,TNM stage,tumor size and serum carcinoembryonic antigen baseline level(P<0.05),but not with age,sex,tumor site,differentiation degree and KRAS exon 2 status(P>0.05).Prognostic analysis showed that the serum exosomal circRASGRF2 level was related to the overall survival(OS)of CRC patients.The median OS of low-level group was not reached,and the 1-,3-,and 5-year survival rates were 100.0%,78.8%and 48.1%,respectively,which were better than 47.0 months and 93.7%,51.1%and 14.3%of high-level group(HR=3.438,95%CI:2.097-5.638,P<0.001).Further multivariate analysis showed that the increase of its level was a risk factor for poor prognosis of CRC patients(HR=3.065,95%CI:2.745-5.266,P=0.009).Conclusion The serum exosomal circRASGRF2 level in CRC patients is increased,which is related to poor prognosis and malignant progression indicators,and is expected to become a potential indicator for diagnosis and treatment guidance and prognosis evaluation of CRC.