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非小细胞肺癌患者血清细胞外囊泡源性微小RNA——寻找非侵入性诊断生物标志物

Serum Extracellular Vesicle-Derived miRNAs in Patients with Non-Small Cell Lung Cancer-Search for Non-Invasive Diagnostic Biomarkers.

作者信息

Kryczka Jolanta, Migdalska-Sęk Monika, Kordiak Jacek, Kiszałkiewicz Justyna M, Pastuszak-Lewandoska Dorota, Antczak Adam, Brzeziańska-Lasota Ewa

机构信息

Department of Biomedicine and Genetics, Medical University of Lodz, 92-213 Lodz, Poland.

Clinic of Thoracic Surgery, General and Oncological Surgery, University Clinical Hospital Named after the Military Medical Academy-Central Veterans' Hospital, Medical University of Lodz, 90-549 Lodz, Poland.

出版信息

Diagnostics (Basel). 2021 Mar 3;11(3):425. doi: 10.3390/diagnostics11030425.

Abstract

The aim of the study was a search for diagnostic and/or prognostic biomarkers in patients with non-small cell lung cancer (NSCLC) patients, based on circulating microRNAs (miRs: miR-23a, miR-361, miR-1228 and miR-let7i) in extracellular vesicles (EVs). Serum EVs were isolated from NSCLC patients ( = 31) and control subjects ( = 21). RNA was isolated from EVs and reverse transcription reaction was performed. Relative levels of miR-23a, miR-361, miR-1228 and miR-let7i were assessed in real-time qPCR using TaqMan probes. Analysis was based on the 2-ΔΔCT method. Statistically significant lower levels of miR-23a and miR-let7i were observed among NSCLC patients vs. control group: miR-23a, 0.054 vs. 0.107; miR-let7i, 0.193 vs. 0.369 ( = 0.003, = 0.005, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential of each individual serum EV-derived miRNA with an area under the curve AUC = 0.744 for miR-23a ( = 0.0003), 0.733 for miR-let7i ( = 0.0007). The decreased level of miR-23a in patients correlated with metastasis to lymph nodes and with AJCC tumor staging system. The results demonstrate that miR-23a and miR-let7i may prove clinically useful as significant, non-invasive markers in NSCLC diagnosis. Additionally, changing profile level of miR-23a that correlates with cancer development may be considered as an NSCLC progression marker.

摘要

本研究旨在基于细胞外囊泡(EVs)中循环的微小RNA(miRs:miR - 23a、miR - 361、miR - 1228和miR - let7i),寻找非小细胞肺癌(NSCLC)患者的诊断和/或预后生物标志物。从NSCLC患者(n = 31)和对照受试者(n = 21)中分离血清EVs。从EVs中分离RNA并进行逆转录反应。使用TaqMan探针通过实时定量PCR评估miR - 23a、miR - 361、miR - 1228和miR - let7i的相对水平。分析基于2 - ΔΔCT法。与对照组相比,NSCLC患者中观察到miR - 23a和miR - let7i的水平在统计学上显著降低:miR - 23a,0.054对0.107;miR - let7i,0.193对0.369(分别为P = 0.003,P = 0.005)。受试者工作特征(ROC)曲线分析表明,每个血清EV衍生的miRNA都具有诊断潜力,miR - 23a的曲线下面积AUC = 0.744(P = 0.0003),miR - let7i的曲线下面积AUC = 0.733(P = 0.0007)。患者中miR - 23a水平降低与淋巴结转移及美国癌症联合委员会(AJCC)肿瘤分期系统相关。结果表明,miR - 23a和miR - let7i可能作为NSCLC诊断中有意义的非侵入性标志物在临床上具有实用价值。此外,与癌症发展相关的miR - 23a水平变化谱可被视为NSCLC进展标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3f/7998231/ad62c7569277/diagnostics-11-00425-g001.jpg

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