Zhang Li, Hu Shangshang, Chen Jiasheng, Ma Shasha, Liu Fanghong, Liu Chuanmiao, Gao Yu
Department of Infectious Diseases, First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, 233030, Bengbu, China.
National Clinical Research Center for Infectious Diseases, First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, 233030, Bengbu, China.
Discov Oncol. 2021 Oct 7;12(1):38. doi: 10.1007/s12672-021-00436-3.
A growing number of studies have shown that competitive endogenous RNA (ceRNA) regulatory networks might play important roles during the process of hepatocellular carcinoma (HCC). This study assessed the role of the ceRNA network in immune cell infiltration in HCC. Immune-related gene sets were downloaded from Molecular Signatures Database, and differentially expressed genes were screened based on TCGA HCC transcriptome data. The corresponding miRNAs with low expression and good prognostic implications, and the corresponding lncRNAs with high expression and poor prognostic were identified to construct ceRNA networks. The networks were utilized for clinical correlation analysis and risk model construction, and the CIBERSORT algorithm was applied to assess immune cell infiltration. In this study, the mRNA-miRNA-lncRNA model was used to construct a ceRNA network in HCC using immune-related differentially expressed mRNAs. Assessment of the MIR4435-2HG/hsa-miR-1-3p/MMP9/hsa-miR-29-3p/DUXAP8 ceRNA network axis in HCC showed that a high risk/poor prognosis was significantly correlated with tumor stage and invasion depth. MMP9 was positively correlated with resting M0 macrophages and NK cells and negatively correlated with activated mast cells, resting mast cells, monocytes and activated NK cells. DUXAP8 was positively correlated with M2 macrophages and negatively correlated with MIR4435-2HG, which was positively correlated with M2 macrophages and negatively correlated with activated mast cells, CD8 T cells and follicular helper T cells. The correlation of the MIR4435-2HG/hsa-miR-1-3p/MMP9/hsa-miR-29-3p/DUXAP8 ceRNA network axis with immune cell infiltration provides further information on the mechanism of HCC development. The result might improve our understanding the interactions between immune related genes and non-coding RNAs in the occurrence and development of HCC, and the relevant RNAs might be used as diagnostic and prognostic biomarkers and molecular targets in HCC patients.
越来越多的研究表明,竞争性内源性RNA(ceRNA)调控网络可能在肝细胞癌(HCC)发生过程中发挥重要作用。本研究评估了ceRNA网络在HCC免疫细胞浸润中的作用。从分子特征数据库下载免疫相关基因集,并基于TCGA HCC转录组数据筛选差异表达基因。鉴定出具有低表达和良好预后意义的相应miRNA,以及具有高表达和不良预后的相应lncRNA,以构建ceRNA网络。将这些网络用于临床相关性分析和风险模型构建,并应用CIBERSORT算法评估免疫细胞浸润。在本研究中,使用mRNA-miRNA-lncRNA模型,利用免疫相关差异表达mRNA构建HCC中的ceRNA网络。对HCC中MIR4435-2HG/hsa-miR-1-3p/MMP9/hsa-miR-29-3p/DUXAP8 ceRNA网络轴的评估表明,高风险/不良预后与肿瘤分期和浸润深度显著相关。MMP9与静息M0巨噬细胞和NK细胞呈正相关,与活化肥大细胞、静息肥大细胞、单核细胞和活化NK细胞呈负相关。DUXAP8与M2巨噬细胞呈正相关,与MIR4435-2HG呈负相关,MIR4435-2HG与M2巨噬细胞呈正相关,与活化肥大细胞、CD8 T细胞和滤泡辅助性T细胞呈负相关。MIR4435-2HG/hsa-miR-1-3p/MMP9/hsa-miR-29-3p/DUXAP8 ceRNA网络轴与免疫细胞浸润的相关性为HCC发生发展机制提供了进一步信息。该结果可能有助于提高我们对HCC发生发展过程中免疫相关基因与非编码RNA之间相互作用的理解,并且相关RNA可能用作HCC患者的诊断和预后生物标志物以及分子靶点。