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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

    摘要
  • 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。

     

    Abstract:
    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.

     

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