血清外泌体微小RNA可能是一种用于识别非小细胞肺癌软脑膜转移的新型液体活检手段。
Serum Exosomal miRNA Might Be a Novel Liquid Biopsy to Identify Leptomeningeal Metastasis in Non-Small Cell Lung Cancer.
作者信息
Xu Qiuli, Ye Liang, Huang Litang, Zhou Li, Chen Xi, Ye Mingxiang, Wu Guannan, Zhan Ping, Lv Tangfeng, Song Yong
机构信息
Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Southeast University, Sch Med, Nanjing, Jiangsu, People's Republic of China.
Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
出版信息
Onco Targets Ther. 2021 Apr 1;14:2327-2335. doi: 10.2147/OTT.S291611. eCollection 2021.
PURPOSE
The survival time of patients with leptomeningeal metastasis (LM) of lung cancer is very short, and the clinical characteristics of LM are varied, making the clinical diagnosis difficult. At present, a positive CSF fluid (CSF) cytology result remains the gold standard for diagnosing LM in lung cancer; however, the process of collecting CSF is traumatic and far less convenient than blood collection. With the development in technology, an increasing number of studies prefer to use liquid biopsy to diagnose or predict the occurrence of the disease. Therefore, we aimed to explore whether serum exosomal miRNA can replace miRNA from CSF to identify or predict the occurrence of LM.
PATIENTS AND METHODS
Herein, four pairs of serum and CSF samples were collected at four different time points from a patient with LM from non-small cell lung cancer (NSCLC). Serum and CSF exosomes were extracted. Western blot (CD63, TSG101) and electron microscope analyses were used to verify exosome extraction, after which exosomal miRNA sequencing was performed. Next, exosomal miRNA from serum and CSF samples from seven patients with LM and 30 patients without LM were collected for validation.
RESULTS
Sequencing results of serum exosomal miRNA and CSF exosomal miRNA showed that there were 44 exosomal miRNAs stably co-expressed at four different time points. Then, three common miRNAs related to LM were found (hsa-miR-483-5p, hsa-miR-423-5p, and hsa-miR-342-5p). Subsequently, exosomal miRNA was extracted from serum and CSF samples from seven patients with LM and 30 patients without LM for verification, and the expression of these exosomal miRNA was detected. The results showed that miRNA-483-5p and miRNA-342-5p significantly differed in LM-/+ patients (P = 0.0142 and P = 0.0031, respectively), whereas miRNA-423-5p had no difference (P = 0.0921). Additionally, as the symptoms improved, the expression of these miRNAs decreased or remained stable.
CONCLUSION
Serum exosomal miRNA (hsa-miR-483-5p, and hsa-miR-342-5p) may be involved in LM of lung cancer and may replace CSF to predict LM in NSCLC.
目的
肺癌软脑膜转移（LM）患者的生存时间非常短，且LM的临床特征多样，导致临床诊断困难。目前，脑脊液（CSF）细胞学检查结果呈阳性仍是诊断肺癌LM的金标准；然而，采集CSF的过程具有创伤性，远不如采集血液方便。随着技术的发展，越来越多的研究倾向于使用液体活检来诊断或预测疾病的发生。因此，我们旨在探讨血清外泌体miRNA是否可以替代CSF中的miRNA来识别或预测LM的发生。
患者和方法
在此，从一名非小细胞肺癌（NSCLC）伴LM的患者在四个不同时间点采集了四对血清和CSF样本。提取血清和CSF外泌体。使用蛋白质免疫印迹法（CD63、TSG101）和电子显微镜分析来验证外泌体的提取，之后进行外泌体miRNA测序。接下来，收集7例LM患者和30例无LM患者的血清和CSF样本中的外泌体miRNA进行验证。
结果
血清外泌体miRNA和CSF外泌体miRNA的测序结果表明，在四个不同时间点有44种外泌体miRNA稳定共表达。然后，发现了三种与LM相关的常见miRNA（hsa-miR-483-5p、hsa-miR-423-5p和hsa-miR-342-5p）。随后，从7例LM患者和30例无LM患者的血清和CSF样本中提取外泌体miRNA进行验证，并检测这些外泌体miRNA的表达。结果显示，miRNA-483-5p和miRNA-342-5p在有/无LM的患者中存在显著差异（分别为P = 0.0142和P = 0.0031），而miRNA-
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