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循环血清外泌体长链非编码RNA FOXD2-AS1、NRIR和XLOC_009459作为结直肠癌的诊断生物标志物

Circulating Serum Exosomal Long Non-Coding RNAs FOXD2-AS1, NRIR, and XLOC_009459 as Diagnostic Biomarkers for Colorectal Cancer.

作者信息

Yu Miao, Song Xing-Guo, Zhao Ya-Jing, Dong Xiao-Han, Niu Li-Min, Zhang Zhi-Jun, Shang Xiao-Ling, Tang You-Yong, Song Xian-Rang, Xie Li

机构信息

Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

出版信息

Front Oncol. 2021 Mar 12;11:618967. doi: 10.3389/fonc.2021.618967. eCollection 2021.

Abstract

BACKGROUND

Exosomes derived from cancer cells encapsulate various kinds of tumor-specific molecules and thus can interact with adjacent or distant cells to mediate information exchange. Long non-coding RNAs (lncRNAs) in exosomes have the potential as diagnostic and prognostic biomarkers in different types of cancers. The current study was aimed to identify circulating exosomal lncRNAs for the diagnosis of colorectal cancer (CRC).

METHODS

Exosomes were isolated from the serum by ultracentrifugation and verified by transmission electron microscope (TEM), qNano, and immunoblotting. Exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 were selected by lncRNA microarray and validated by qPCR in 203 CRC patients and 201 healthy donors. The receiver operating characteristic curve (ROC) was used to assess the diagnostic efficiency of serum exosomal lncRNAs.

RESULTS

Exosomal FOXD2-AS1, NRIR, and XLOC_009459 (TCONS_00020073) levels were significantly upregulated in 203 CRC patients and 80 early-stage CRC patients compared to 201 healthy donors, possessing the area under the curve (AUC) of 0.728, 0.660, and 0.682 for CRC, as well as 0.743, 0.660, and 0.689 for early-stage CRC, respectively. Notably, their combination demonstrated the markedly elevated AUC of 0.736 for CRC and 0.758 for early-stage CRC, indicating their potential as diagnostic biomarkers for CRC.

CONCLUSIONS

Our data suggested that exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 act as the promising biomarkers for the diagnostics of CRC and early-stage CRC.

摘要

背景

癌细胞衍生的外泌体包裹着各种肿瘤特异性分子,因此能够与相邻或远处的细胞相互作用,介导信息交换。外泌体中的长链非编码RNA(lncRNA)有潜力成为不同类型癌症的诊断和预后生物标志物。本研究旨在鉴定用于诊断结直肠癌(CRC)的循环外泌体lncRNA。

方法

通过超速离心从血清中分离外泌体,并通过透射电子显微镜(TEM)、qNano和免疫印迹进行验证。通过lncRNA微阵列选择外泌体lncRNA FOXD2-AS1、NRIR和XLOC_009459,并在203例CRC患者和201例健康供体中通过qPCR进行验证。采用受试者工作特征曲线(ROC)评估血清外泌体lncRNA的诊断效率。

结果

与201例健康供体相比,203例CRC患者和80例早期CRC患者中外泌体FOXD2-AS1、NRIR和XLOC_009459(TCONS_00020073)水平显著上调,CRC的曲线下面积(AUC)分别为0.728、0.660和0.682,早期CRC分别为0.743、0.660和0.689。值得注意的是,它们的组合显示CRC的AUC显著提高至0.736,早期CRC为0.758,表明它们作为CRC诊断生物标志物的潜力。

结论

我们的数据表明,外泌体lncRNA FOXD2-AS1、NRIR和XLOC_009459有望成为CRC和早期CRC诊断的生物标志物。

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