外泌体来源的circRNA_051778在肺腺癌性恶性胸腔积液和结核性胸腔积液中的表达及作用研究  

Expression of circRNA_051778 in Lung Adenocarcinoma-Associated Malignant and Tuberculous Pleural Effusions and Its Clinical Significance

作　　者：叶芷杉 农雪萍 王艳云[3] 车光璐 周斌[3] 黄建华[5] 张林[1,3] YE Zhishan;NONG Xueping;WANG Yanyun;CHE Guanglu;ZHOU Bin;HUANG Jianhua;ZHANG Lin(West China School of Basic Medical Sciences and Forensic Medicine,Sichuan University,Chengdu 610041,China;Department of Pathology,Jiangxi Chest Hospital,Nanchang 330006,China;Laboratory of Molecular and Translational Medicine,West China Second University Hospital,Sichuan University,Chengdu 610041,China;Department of Laboratory Medicine,West China Second University Hospital,Sichuan University,Chengdu 610041,China;Department of Respiratory and Critical Care Medicine,Jiangxi Chest Hospital,Nanchang 330006,China)

机构地区：[1]四川大学华西基础医学与法医学院,成都610041 [2]江西省胸科医院病理科,南昌330006 [3]四川大学华西第二医院转化医学中心-分子与转化医学实验室,成都610041 [4]四川大学华西第二医院检验科,成都610041 [5]江西省胸科医院呼吸与重症医学科,南昌330006

出　　处：《四川大学学报（医学版）》2024年第5期1254-1263,共10页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.81974365)资助。

摘　　要：目的分析circRNA_051778在肺腺癌性恶性胸腔积液(LA-MPE)和结核性胸腔积液(TPE)样本中的临床意义。方法本研究为横断面研究。2018年10月–2019年9月间于江西省胸科医院共募集212例患者,收集患者入院第1天胸腔积液和/或血浆。使用circRNA微阵列分析LA-MPE和TPE样本中的外泌体环状RNA(circRNAs),通过微滴式数字PCR验证差异表达环状RNA(DECs)。此外,构建可能的circRNA-miRNA-mRNA网络,并进行了GO(Gene Ontology)分析和KEGG(Kyoto Encyclopedia of Genes and Genomes)通路分析,以预测DECs的功能。通过二分类逻辑回归和受试者工作特征曲线评估circRNA_051778的诊断价值。结果circRNA_051778的表达水平在LA-MPE样本中为(3.92±0.48)拷贝数/100 ng cDNA,在TPE样本中为(21.53±2.22)拷贝数/100 ng cDNA。与TPE相比,LA-MPE样本中的circRNA_051778下调(P<0.001)。circRNA_051778的潜在靶标富集于GTPase活性正调控、细胞质、蛋白结合和癌症相关通路中。circRNA_051778与液基薄层细胞学检查(TCT)、红细胞沉降率(ESR)和结核抗体(TBA)联合检测的曲线下面积为0.98(95%置信区间:0.97~1.00),敏感性为88.0%,特异性为100.0%。结论外泌体中的circRNA_051778在LA-MPE中下调,GO和KEGG分析结果显示其可能在癌症的发展中发挥作用,与TCT、ESR、TBA联合有望作为LA-MPE和TPE鉴别诊断标志物。Objective To investigate the expression and clinical significance of circular RNA(circRNA)051778 in lung adenocarcinoma-malignant pleural effusion(LA-MPE)and tuberculous pleural effusion(TPE).Methods This is a cross-sectional study.A total of 212 patients were recruited from the Jiangxi Chest Hospital between October 2018 and September 2019,and their pleural effusion samples and/or plasma samples were collected.The exosomal circRNA profile was sketched by circRNA microarray.Differentially expressed circRNAs(DECs)were verified by droplet digital PCR.In addition,a putative circRNA-miRNA-mRNA network was constructed,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed to predict the functions of the DECs.The diagnostic value of circRNA_051778 was evaluated by binary logistic regression and receiver operating characteristic curve.Results The expression level of circRNA_051778 in the LA-MPE samples was(3.92±0.48)copies/100 ng cDNA,while that in the TPE samples was(21.53±2.22)copies/100 ng cDNA.Compared to that in the TPE samples,circRNA_051778 was significantly downregulated in the LA-MPE samples(P<0.001).The potential targets of circRNA_051778 were enriched in positive regulation of GTPase activity,cytoplasm,protein binding,and cancer-related pathways.The area under the curve(AUC)for the combined assessment of circRNA_051778 with liquid-based thin-layer cytology(TCT),erythrocyte sedimentation rate(ESR),and tuberculosis antibody(TBA)was 0.98(95%confidence interval:0.97-1.00),with the sensitivity being 88.0%and the specificity being 100.0%.Conclusion Exosomal circRNA_051778 is downregulated in LA-MPE.According to the findings from the GO and KEGG analyses,exosomal circRNA_051778 may play a role in cancer development and has the potential to serve as a marker for differential diagnostic of LA-MPE and TPE when it is used in combination with TCT,ESR,and TBA.

关 键 词：环状RNA 外泌体 胸腔积液 肺结核 肺腺癌 

分 类 号：R734.2[医药卫生—肿瘤]