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肿瘤来源的外泌体长链非编码RNA作为前列腺癌有前景的诊断生物标志物

Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer.

作者信息

Wang Yu-Hui, Ji Jia, Wang Bi-Cheng, Chen Hao, Yang Zhong-Hua, Wang Kun, Luo Chang-Liang, Zhang Wu-Wen, Wang Fu-Bing, Zhang Xiao-Lian

机构信息

Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.

Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China.

出版信息

Cell Physiol Biochem. 2018;46(2):532-545. doi: 10.1159/000488620. Epub 2018 Mar 26.

Abstract

BACKGROUND/AIMS: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa).

METHODS

A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value.

RESULTS

Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone.

CONCLUSION

The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.

摘要

背景/目的:血液中循环的外泌体长链非编码RNA(lncRNA)正逐渐成为肿瘤诊断中具有临床应用价值的非侵入性生物标志物。然而,正常细胞也能分泌外泌体,因此获取肿瘤来源的外泌体是更好地了解其在癌症诊断中作用的前提条件。在本研究中,建立了一种双抗体功能化免疫亲和系统,用于分离外泌体并研究其lncRNA表达模式及在前列腺癌(PCa)中的临床意义。

方法

使用市售试剂盒分离总外泌体,然后通过双抗体功能化免疫亲和系统进行纯化。采用RT-qPCR检测外泌体lncRNA的表达。绘制受试者工作特征(ROC)曲线以评估诊断价值。

结果

肿瘤来源外泌体中两种lncRNA的表达水平显著高于总外泌体中的表达水平。良性前列腺增生(BPH)中SAP30L-AS1水平上调,PCa中SChLAP1水平显著高于BPH和健康个体。ROC曲线下面积表明,SAP30L-AS1和SChLAP1具有区分PCa与对照的足够诊断价值。两种lncRNA分别与前列腺特异性抗原(PSA)联合具有中等区分能力。SAP30L-AS1表达水平与PSA值和肿瘤侵袭有关。SChLAP1在Gleason评分较高的患者中表达显著更高,并且在PSA浓度处于灰色区域时也能有效区分BPH和PCa。

结论

通过双抗体功能化免疫亲和系统分离肿瘤来源的外泌体并检测血浆中的lncRNA,可能会鉴定出具有潜在诊断效用的合适生物标志物。

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