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鉴定与干扰素治疗后肝细胞癌复发相关的 miRNAs、mRNAs、lncRNAs 和 circRNAs。

Identification of miRNAs, mRNAs, lncRNAs, and circRNAs associated with hepatocellular carcinoma recurrence after interferon treatment.

机构信息

Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, P.R. China.

出版信息

J Biol Regul Homeost Agents. 2021 Aug 27;35(4). doi: 10.23812/21-173-A. Epub 2021 Jul 23.

Abstract

To study the molecular mechanism of interferon-alpha (IFN-α) in the treatment of hepatocellular carcinoma (HCC) and the molecular markers that can predict the therapeutic effect, differentially expressed (DE)-miRNAs, -mRNAs, -lncRNAs, and -circRNAs were screened between 12 samples collected from 4 patients who had not received treatment (control), 4 patients who had received recombinant human interferon a-2b treatment (case1), and 4 patients who had relapsed after receiving recombinant human interferon a-2b treatment (case2). Enrichment analyses were performed to determine the principal functions of the DE-RNAs. We also constructed protein-protein interactions (PPI) and competing endogenous RNA (ceRNA) networks. In addition, a series-cluster analysis was performed to analyze changes in gene expression across different groups of HCC. Furthermore, the expression of the genes were verified in the Cancer Genome Atlas (TCGA) database. A total of 36 union DE-miRNAs, 175 union DE-mRNAs, 65 union DE-lncRNAs, and 52 union DE-circRNAs were obtained between the control vs case1, and case2 vs case1 groups. DE-mRNAs were mainly involved in the mitochondrial inner membrane. DE-circRNAs were mainly enriched in the Golgi apparatus. ceRNA network contained 68 DE-mRNAs, 26 DE-miRNAs, 45 DE-lncRNAs, and 23 DE-circRNAs. A total of 24 DE-miRNAs, 175 DE-mRNAs, 65 DE-lncRNAs, and 52 DE-circRNAs were classified into eight profiles, respectively. A total of 26 genes showed a significant correlation with prognosis of HCC (p < 0.05). Some genes may be used to predict the efficacy of IFN-α in the treatment of HCC. The results may lay a foundation for investigating the different sensitivities of IFN-α in the treatment of HCC.

摘要

为了研究干扰素-α(IFN-α)治疗肝细胞癌(HCC)的分子机制和可以预测治疗效果的分子标志物,我们在未接受治疗(对照)、接受重组人干扰素 a-2b 治疗(病例 1)和接受重组人干扰素 a-2b 治疗后复发(病例 2)的 4 名患者的 12 个样本之间筛选了差异表达(DE)的-miRNAs、-mRNAs、-lncRNAs 和 -circRNAs。进行富集分析以确定 DE-RNAs 的主要功能。我们还构建了蛋白质-蛋白质相互作用(PPI)和竞争内源性 RNA(ceRNA)网络。此外,还进行了一系列聚类分析以分析 HCC 不同组之间基因表达的变化。此外,在癌症基因组图谱(TCGA)数据库中验证了基因的表达。在对照与病例 1 组和病例 2 与病例 1 组之间共获得了 36 个联合 DE-miRNAs、175 个联合 DE-mRNAs、65 个联合 DE-lncRNAs 和 52 个联合 DE-circRNAs。DE-mRNAs 主要参与线粒体内膜。DE-circRNAs 主要富集在高尔基体中。ceRNA 网络包含 68 个 DE-mRNAs、26 个 DE-miRNAs、45 个 DE-lncRNAs 和 23 个 DE-circRNAs。共有 24 个 DE-miRNAs、175 个 DE-mRNAs、65 个 DE-lncRNAs 和 52 个 DE-circRNAs分别分为八个谱系。共有 26 个基因与 HCC 的预后显著相关(p < 0.05)。一些基因可能用于预测 IFN-α治疗 HCC 的疗效。研究结果可能为研究 IFN-α治疗 HCC 的不同敏感性奠定基础。

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