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使用基于神经网络的框架Cascaded Wx在肺腺癌患者中鉴定新型微小RNA预后标志物

Identification of Novel microRNA Prognostic Markers Using Cascaded Wx, a Neural Network-Based Framework, in Lung Adenocarcinoma Patients.

作者信息

Kim Jeong Seon, Chun Sang Hoon, Park Sungsoo, Lee Sieun, Kim Sae Eun, Hong Ji Hyung, Kang Keunsoo, Ko Yoon Ho, Ahn Young-Ho

机构信息

Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea.

Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea.

出版信息

Cancers (Basel). 2020 Jul 14;12(7):1890. doi: 10.3390/cancers12071890.

Abstract

The evolution of next-generation sequencing technology has resulted in a generation of large amounts of cancer genomic data. Therefore, increasingly complex techniques are required to appropriately analyze this data in order to determine its clinical relevance. In this study, we applied a neural network-based technique to analyze data from The Cancer Genome Atlas and extract useful microRNA (miRNA) features for predicting the prognosis of patients with lung adenocarcinomas (LUAD). Using the Cascaded Wx platform, we identified and ranked miRNAs that affected LUAD patient survival and selected the two top-ranked miRNAs (miR-374a and miR-374b) for measurement of their expression levels in patient tumor tissues and in lung cancer cells exhibiting an altered epithelial-to-mesenchymal transition (EMT) status. Analysis of miRNA expression from tumor samples revealed that high miR-374a/b expression was associated with poor patient survival rates. In lung cancer cells, the EMT signal induced miR-374a/b expression, which, in turn, promoted EMT and invasiveness. These findings demonstrated that this approach enabled effective identification and validation of prognostic miRNA markers in LUAD, suggesting its potential efficacy for clinical use.

摘要

下一代测序技术的发展产生了大量癌症基因组数据。因此,需要越来越复杂的技术来恰当地分析这些数据,以确定其临床相关性。在本研究中,我们应用了一种基于神经网络的技术来分析来自癌症基因组图谱的数据,并提取有用的微小RNA(miRNA)特征,以预测肺腺癌(LUAD)患者的预后。使用级联Wx平台,我们鉴定并对影响LUAD患者生存的miRNA进行了排名,并选择了排名前两位的miRNA(miR-374a和miR-374b)来测量它们在患者肿瘤组织和上皮-间质转化(EMT)状态改变的肺癌细胞中的表达水平。对肿瘤样本中miRNA表达的分析表明,高miR-374a/b表达与患者低生存率相关。在肺癌细胞中,EMT信号诱导miR-374a/b表达,进而促进EMT和侵袭性。这些发现表明,这种方法能够有效地识别和验证LUAD中的预后miRNA标志物,提示其临床应用的潜在疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/716a/7409139/a3ca73286fe8/cancers-12-01890-g001.jpg

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