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基于血清外泌体长链非编码 RNA 标志物panel 的膀胱癌诊断和复发预测评估。

Evaluation of serum exosomal LncRNA-based biomarker panel for diagnosis and recurrence prediction of bladder cancer.

机构信息

Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China.

Tumor Marker Detection Engineering Laboratory of Shandong Province, Jinan, Shandong, China.

出版信息

J Cell Mol Med. 2019 Feb;23(2):1396-1405. doi: 10.1111/jcmm.14042. Epub 2018 Nov 23.

Abstract

Exosomes are small membrane vesicles released by many cells. These vesicles can mediate cellular communications by transmitting active molecules including long non-coding RNAs (lncRNAs). In this study, our aim was to identify a panel of lncRNAs in serum exosomes for the diagnosis and recurrence prediction of bladder cancer (BC). The expressions of 11 candidate lncRNAs in exosome were investigated in training set (n = 200) and an independent validation set (n = 320) via quantitative real-time PCR. A three-lncRNA panel (PCAT-1, UBC1 and SNHG16) was finally identified by multivariate logistic regression model to provide high diagnostic accuracy for BC with an area under the receiver-operating characteristic curve (AUC) of 0.857 and 0.826 in training set and validation set, respectively, which was significantly higher than that of urine cytology. The corresponding AUCs of this panel for patients with Ta, T1 and T2-T4 were 0.760, 0.827 and 0.878, respectively. In addition, Kaplan-Meier analysis showed that non-muscle-invasive BC (NMIBC) patients with high UBC1 expression had significantly lower recurrence-free survival (P = 0.01). Multivariate Cox analysis demonstrated that UBC1 was independently associated with tumour recurrence of NMIBC (P = 0.018). Our study suggested that lncRNAs in serum exosomes may serve as considerable diagnostic and prognostic biomarkers of BC.

摘要

外泌体是许多细胞释放的小膜囊泡。这些囊泡可以通过传递包括长链非编码 RNA(lncRNA)在内的活性分子来介导细胞间通讯。在这项研究中,我们的目的是鉴定血清外泌体中的一组 lncRNA,用于膀胱癌(BC)的诊断和复发预测。通过定量实时 PCR 研究了训练集(n=200)和独立验证集(n=320)中外泌体中 11 个候选 lncRNA 的表达。通过多元逻辑回归模型最终确定了一个由三个 lncRNA 组成的 panel(PCAT-1、UBC1 和 SNHG16),为 BC 提供了较高的诊断准确性,其在训练集和验证集中的受试者工作特征曲线(ROC)下面积(AUC)分别为 0.857 和 0.826,明显高于尿细胞学检查。该 panel 对 Ta、T1 和 T2-T4 患者的 AUC 分别为 0.760、0.827 和 0.878。此外,Kaplan-Meier 分析表明,高 UBC1 表达的非肌肉浸润性 BC(NMIBC)患者的无复发生存率(RFS)显著降低(P=0.01)。多因素 Cox 分析表明,UBC1 与 NMIBC 的肿瘤复发独立相关(P=0.018)。我们的研究表明,血清外泌体中的 lncRNA 可能作为 BC 有价值的诊断和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/6349164/12c00052d357/JCMM-23-1396-g001.jpg

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