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阐明肝细胞癌的进展:一种新的预后 miRNA-mRNA 网络和特征分析。

Elucidating hepatocellular carcinoma progression: a novel prognostic miRNA-mRNA network and signature analysis.

机构信息

Clinical Research Center, Shijiazhuang Fifth Hospital, Shijiazhuang, Hebei, China.

出版信息

Sci Rep. 2024 Feb 29;14(1):5042. doi: 10.1038/s41598-024-55806-y.

Abstract

There is increasing evidence that miRNAs play an important role in the prognosis of HCC. There is currently a lack of acknowledged models that accurately predict patient prognosis. The aim of this study is to create a miRNA-based model to precisely forecast a patient's prognosis and a miRNA-mRNA network to investigate the function of a targeted mRNA. TCGA miRNA dataset and survival data of HCC patients were downloaded for differential analysis. The outcomes of variance analysis were subjected to univariate and multivariate Cox regression analyses and LASSO analysis. We constructed and visualized prognosis-related models and subsequently used violin plots to probe the function of miRNAs in tumor cells. We predicted the target mRNAs added those to the String database, built PPI protein interaction networks, and screened those mRNA using Cytoscape. The hub mRNA was subjected to GO and KEGG analysis to determine its biological role. Six of them were associated with prognosis: hsa-miR-139-3p, hsa-miR-139-5p, hsa-miR-101-3p, hsa-miR-30d-5p, hsa-miR-5003-3p, and hsa-miR-6844. The prognostic model was highly predictive and consistently performs, with the C index exceeding 0.7 after 1, 3, and 5 years. The model estimated significant differences in the Kaplan-Meier plotter and the model could predict patient prognosis independently of clinical indicators. A relatively stable miRNA prognostic model for HCC patients was constructed, and the model was highly accurate in predicting patients with good stability over 5 years. The miRNA-mRNA network was constructed to explore the function of mRNA.

摘要

越来越多的证据表明 miRNAs 在 HCC 的预后中发挥着重要作用。目前还没有公认的模型能够准确预测患者的预后。本研究旨在构建一个基于 miRNA 的模型,以精确预测患者的预后,并构建一个 miRNA-mRNA 网络来研究靶向 mRNA 的功能。下载 TCGA miRNA 数据集和 HCC 患者的生存数据进行差异分析。方差分析的结果进行单因素和多因素 Cox 回归分析和 LASSO 分析。我们构建并可视化了与预后相关的模型,然后使用小提琴图探讨了 miRNA 在肿瘤细胞中的功能。我们预测了添加到 String 数据库中的靶 mRNA,构建了 PPI 蛋白相互作用网络,并使用 Cytoscape 筛选了那些 mRNA。对 hub mRNA 进行 GO 和 KEGG 分析,以确定其生物学作用。其中 6 个与预后相关:hsa-miR-139-3p、hsa-miR-139-5p、hsa-miR-101-3p、hsa-miR-30d-5p、hsa-miR-5003-3p 和 hsa-miR-6844。该预后模型具有高度的预测能力,且一致性表现良好,C 指数在 1、3 和 5 年后均超过 0.7。在 Kaplan-Meier 绘图仪中,该模型估计差异显著,并且可以独立于临床指标预测患者的预后。构建了一个相对稳定的 HCC 患者 miRNA 预后模型,该模型在 5 年内具有良好的稳定性,预测患者的准确性较高。构建了 miRNA-mRNA 网络来探讨 mRNA 的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/283c/10904818/3a124d0e84a0/41598_2024_55806_Fig1_HTML.jpg

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