血清外泌体hsa_circ_0004390预测上皮性卵巢癌铂类耐药及预后的临床研究  

Clinical study of serumexosome hsa_circ_0004390 in predicting platinum resistance and prognosis of epithelial ovarian cancer

作　　者：王娟娟[1] 唐小慧[1] 唐鸣[1] WANG Juanjuan;TANG Xiaohui;TANG Ming(Department of Oncology,Qidong People s Hospital(Qidong Hospital Affiliated to Nantong University),Nantong 226200,China)

机构地区：[1]启东市人民医院(南通大学附属启东医院)肿瘤一科,江苏南通226200

出　　处：《临床肿瘤学杂志》2023年第2期138-144,共7页Chinese Clinical Oncology

摘　　要：目的探讨上皮性卵巢癌(EOC)患者血清外泌体hsa_circ_0004390与化疗耐药和预后的关系。方法收集2017年1月至12月启东市人民医院(南通大学附属启东医院)肿瘤一科收治的87例原发性EOC患者癌组织及血清样本,另外招募85例健康女性志愿者,获取对照血清样本。将辅助化疗无效或6个月内疾病发生进展的患者纳入耐药组(n=30),其余患者设为敏感组(n=57)。10例接受根治性手术患者的组织样本进行下一代测序(NGS)以筛选circRNA基因谱。实时荧光定量PCR(qPCR)法验证候选circRNAs基因的表达水平。结果在NGS鉴定出的circRNA基因中,共285个circRNA在耐药组和敏感组EOC组织中存在表达差异(P<0.05)。验证后发现5例耐药组EOC组织中只有hsa_circ_0004390(P=0.004)和hsa_circ_0006276(P=0.045)相对表达量高于敏感组,因此选择这两种基因进行分析。qPCR检测结果显示,与对照组比较,EOC组患者血清外泌体hsa_circ_0004390[2.57(1.47,2.99)vs.0.94(0.61,1.35),P<0.001]和hsa_circ_0006276[1.26(1.03,1.46)vs.0.87(0.67,1.39),P=0.001]相对表达量均显著升高。受试者工作特征(ROC)曲线进一步分析发现血清外泌体hsa_circ_0004390对EOC的诊断效能更高。耐药组患者血清外泌体hsa_circ_0004390表达显著高于敏感组患者[3.07(2.66,3.66)vs.1.69(1.23,2.59),P<0.001],血清外泌体hsa_circ_0006276与铂类化疗反应无关(P>0.05)。进一步校正客观干扰因素后,发现血清外泌体hsa_circ_0004390是影响EOC患者铂类化疗反应的独立因素(P<0.05)。血清外泌体hsa_circ_0004390表达低水平(<2.57)亚组患者OS较高水平亚组(≥2.57)患者更优(P=0.005)。结论血清外泌体hsa_circ_0004390有助于预测EOC患者对基于铂类方案的化疗反应以及生存预后,可能为EOC治疗提供新的靶点。Objective To investigate the relationship between serum exosome hsa_circ_0004390 and chemotherapy resistance and adverse prognosis in patients with epithelial ovarian cancer(EOC).Methods From January to December 2017,the cancer tissue and serum samples of 87 patients with primary EOC were collected from the First Department of Oncology of Qidong People’s Hospital(QidongHospital affiliated to Nantong University),and 85 healthy female volunteers were recruited to obtain control serum samples.The patients who were ineffective in adjuvant chemotherapy or had disease progression within 6 months were included in the drug resistance group(n=30),and the other patients were included in the sensitive group(n=57).Tissue samples from 10 patients undergoing radical surgery were used for next generation sequencing(NGS)to screen the circRNA gene spectrum.The expression level of candidate circRNAs gene was verified by real-time fluorescent quantitative PCR(qPCR).Results Among the circRNA genes identified by NGS,a total of 285 circrnas expressed differently in the EOC tissues of the drug-resistant group and the sensitive group(P<0.05).After verification,the relative expression levels of hsa_circ_0004390(P=0.004)and hsa_circ_0006276(P=0.045)in the EOC tissue of the 5 patients in the drug-resistant group were higher than sensitive group,so we chose these two genes for further analysis.q-PCR showed that compared with the control group,the relative expression of serum exosomalhsa_circ_0004390[2.57(1.47,2.99)vs.0.94(0.61,1.35),P<0.001]and hsa_circ_0006276[1.26(1.03,1.46)vs.0.87(0.67,1.39),P=0.001]in EOC group were significantly increased.Further analysis of the working characteristic curve of the subjects found that the serum exosomalhsa_circ_0004390 was more effective in the diagnosis of EOC.In addition,the expression of serum exosomalhsa_circ_0004390 in patients with drug resistance was significantly higher than that in patients with sensitivity group[3.07(2.66,3.66)vs.1.69(1.23,2.59),P<0.001].However,serum exosomalhsa_circ_000627

关 键 词：上皮性卵巢癌 化疗耐药 不良预后 hsa_circ_0004390 

分 类 号：R737.31[医药卫生—肿瘤]