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手术前后外泌体 miRNA 谱分析揭示了肺腺癌潜在的诊断和预后标志物。

Exosomal miRNA profiling before and after surgery revealed potential diagnostic and prognostic markers for lung adenocarcinoma.

机构信息

Department of Respiratory and Critical Care, Chinese PLA General Hospital, Beijing 100853, China.

Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2020 Mar 18;52(3):281-293. doi: 10.1093/abbs/gmz164.

Abstract

Exosome is a crucial manner for cancer cell to cell communication and circulating exosomes sever as promising diagnostic and prognostic markers for various types of diseases. A predominant type of cargo of exosome is small RNAs, especially miRNAs. Here, we profiled plasma exosomal miRNAs of six lung adenocarcinoma patients before and after surgery, as well as six healthy individuals as normal control. Our profiling revealed 38 upregulated and 37 downregulated exosomal miRNAs in the plasma of lung adenocarcinoma patients. Additionally, we found that most upregulated miRNAs were increased in the lung adenocarcinoma samples of TCGA database. We further evaluated the correlation between the upregulated exosomal miRNAs and overall survival with Kaplan-Meier survival analysis using online databases. Our results suggested that exosomal miR-151a-5p, miR-10b-5p, miR-192-5p, miR-106b-3p, and miR-484 are potential prognostic markers for lung adenocarcinoma. Importantly, we validated candidate miRNAs in lung adenocarcinoma patients before and after surgery as well as in healthy controls and found that miR-484 was significantly increased in the plasma of lung adenocarcinoma patients and strikingly decreased post-surgery. Hence, we provided novel information on lung adenocarcinoma-derived exosomal miRNA and potential non-invasive diagnostic and prognostic markers for lung adenocarcinoma.

摘要

外泌体是癌细胞间通讯的重要方式,循环外泌体可作为各种疾病有前途的诊断和预后标志物。外泌体的主要 cargo 之一是小 RNA,尤其是 miRNAs。在这里,我们对 6 名肺癌患者手术前后的血浆外泌体 miRNAs 以及 6 名健康个体进行了分析。我们的分析显示,肺癌患者血浆中有 38 个上调和 37 个下调的外泌体 miRNAs。此外,我们发现 TCGA 数据库中大多数上调的 miRNAs 在肺腺癌样本中均有增加。我们进一步使用在线数据库通过 Kaplan-Meier 生存分析评估了上调的外泌体 miRNAs 与总生存期之间的相关性。我们的结果表明,外泌体 miR-151a-5p、miR-10b-5p、miR-192-5p、miR-106b-3p 和 miR-484 是肺腺癌的潜在预后标志物。重要的是,我们在肺癌患者手术前后以及健康对照者中验证了候选 miRNAs,发现 miR-484 在肺腺癌患者的血浆中显著增加,手术后显著降低。因此,我们提供了关于肺癌衍生的外泌体 miRNA 的新信息,并为肺腺癌提供了潜在的非侵入性诊断和预后标志物。

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