Evaluating the presence of deregulated tumoral onco-microRNAs in serum-derived exosomes of gastric cancer patients as noninvasive diagnostic biomarkers

Houman Kahroba, N. Samadi, M. Mostafazadeh, Mohammad Saeid Hejazi, M. Sadeghi, S. Hashemzadeh, A. E. Eftekhar Sadat, A. Karimi
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引用次数: 8

Abstract

Introduction: Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for different types of cancers. We aim to detect gastric cancer (GC)-specific miRNAs in serum exosomes with diagnostic potential. Methods: A pair of 43 tumor and tumor-adjacent tissue biopsies obtained from GC patients, also 5 mL peripheral blood (following 12h fasting) were collected from the same patients and healthy controls (HCs). QIAGEN miRCURY LNA miRNA Focus PCR Panel applied to screen differentially expressed onco-miRNAs. The candidate miRNAs with the highest fold changes proceeded for validation by qRT-PCR in individuals. Results: We identified that exosomal miR-10a-5p, miR-19b-3p, miR-215-5p, and miR-18a-5p were significantly upregulated in GC patient’s exosomes in contrast to HCs exosomes, Roc curve analysis indicated area under the ROC curve (AUC) of 0.801, 0.721, 0.780 and 0.736 respectively. The Roc curve analysis for the combined signature of four exosomal miRNAs indicated AUC of 0.813. Also, Spearman's correlation coefficients indicated that the miRNA expression is highly correlated between tumor and exosome. Conclusion: Herein, we specifically identified four miRNAs in serum exosomes of GC patients for a diagnostic purpose which are directly associated with tumoral miRNA expression profile.
评估胃癌患者血清来源外泌体中不受调控的肿瘤微rna作为无创诊断生物标志物的存在
外泌体microRNAs (miRNAs)是新兴的诊断不同类型癌症的生物标志物。我们的目的是在血清外泌体中检测具有诊断潜力的胃癌(GC)特异性mirna。方法:分别取胃癌患者43例肿瘤及癌旁组织活检,同时取胃癌患者及健康对照(hc)空腹12小时后外周血5 mL。QIAGEN miRCURY miRNA Focus PCR Panel用于筛选差异表达的肿瘤miRNA。fold change最高的候选mirna在个体中进行qRT-PCR验证。结果:我们发现外泌体miR-10a-5p、miR-19b-3p、miR-215-5p和miR-18a-5p在GC患者的外泌体中与hcc外泌体相比显著上调,Roc曲线分析显示Roc曲线下面积(AUC)分别为0.801、0.721、0.780和0.736。四种外泌体mirna联合标记的Roc曲线分析显示AUC为0.813。此外,Spearman相关系数表明miRNA表达在肿瘤和外泌体之间高度相关。结论:本研究在GC患者血清外泌体中特异性鉴定出4种与肿瘤miRNA表达谱直接相关的miRNA,用于诊断目的。
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