Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
J Biol Regul Homeost Agents. 2021 Aug 27;35(4). doi: 10.23812/21-173-A. Epub 2021 Jul 23.
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.
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。
