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肿瘤来源的外泌体 lncRNA GAS5 作为早期非小细胞肺癌诊断的生物标志物。

Tumor-derived exosomal lncRNA GAS5 as a biomarker for early-stage non-small-cell lung cancer diagnosis.

机构信息

Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, China.

Department of Cardiothoracic Surgery, Jingling Hospital, Nanjing Medical University, Nanjing, China.

出版信息

J Cell Physiol. 2019 Nov;234(11):20721-20727. doi: 10.1002/jcp.28678. Epub 2019 Apr 29.

Abstract

Diagnosis and treatment at an early stage may improve survival of non-small-cell lung cancer (NSCLC). Previous studies have found that long noncoding RNA growth arrest-specific transcript 5 (GAS5) is essential to cancer progression. However, the expression and diagnostic value of GAS5 in exosomes (Exo-GAS5) remain unclear. One hundred and four participants were enrolled, including subjects with NSCLC (n = 64) and healthy subjects ( n = 40). The total Exosome Isolation Kit was applied to isolate exosomes from serum. Total RNA was extracted and the AS5 expression was analyzed using quantitative reverse transcription polymerase chain reaction. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic value of Exo-GAS5 in NSCLC. Our data indicated that the Exo-GAS5 was downregulated in patients with NSCLC compared with healthy controls ( p < 0.001). Furthermore, patients with NSCLC with larger tumor size ( p = 0.025) and advanced TNM (T: extent of the primary tumor; N: lymph node involvement; M: metastatic disease) classification ( p = 0.047) showed lower Exo-GAS5 expression. ROC curve analysis using Exo-GAS5 combined with carcinoembryonic antigen showed an area under curve (AUC) of 0.929. Exo-GAS5 could be used to distinguish patients with Stage I NSCLC with an AUC of 0.822. In conclusion, Exo-GAS5 may function as an ideal noninvasive serum-based marker for identifying patients with early NSCLC.

摘要

早期诊断和治疗可能会提高非小细胞肺癌(NSCLC)的生存率。先前的研究发现,长非编码 RNA 生长停滞特异性转录物 5(GAS5)对癌症的进展至关重要。然而,外泌体(Exo-GAS5)中 GAS5 的表达和诊断价值仍不清楚。本研究纳入了 104 名参与者,包括 NSCLC 患者(n=64)和健康对照者(n=40)。应用总外泌体分离试剂盒从血清中分离外泌体。提取总 RNA,采用定量逆转录聚合酶链反应分析 GAS5 的表达。应用受试者工作特征(ROC)曲线分析评估 Exo-GAS5 在 NSCLC 中的诊断价值。我们的数据表明,与健康对照组相比,NSCLC 患者的 Exo-GAS5 表达下调(p<0.001)。此外,肿瘤体积较大(p=0.025)和 TNM 分期较晚(T:原发肿瘤的范围;N:淋巴结受累;M:远处转移)的 NSCLC 患者 Exo-GAS5 表达较低(p=0.047)。ROC 曲线分析显示,Exo-GAS5 联合癌胚抗原的曲线下面积(AUC)为 0.929。Exo-GAS5 可用于鉴别Ⅰ期 NSCLC 患者,AUC 为 0.822。总之,Exo-GAS5 可能是一种理想的、基于血清的非侵入性标志物,可用于识别早期 NSCLC 患者。

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