Zhou Peitao, Zheng Guanglei, Li Yalin, Wu Dehua, Chen Yuhan
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Front Genet. 2020 Sep 4;11:1026. doi: 10.3389/fgene.2020.01026. eCollection 2020.
Immune cells in the tumor microenvironment play a crucial role in regulating tumor progression. The circular RNA (circRNA) regulatory network involved in immune cell infiltration in hepatocellular carcinoma (HCC) remains largely unknown. In this study, the "estimate the proportion of immune and cancer cells" (EPIC) application is used to evaluate the fractions of immune cells, cancer-associated fibroblasts, and endothelial cells in HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Patients with a high macrophage fraction have better overall survival, and macrophage fraction is an independent prognostic factor for HCC. Next, the common differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) between paired tumor and non-tumor tissues are screened out from the TCGA and/or GEO databases. Through spearman correlation analysis, the macrophage-related DEmRNAs are identified to construct a circRNA-miRNA-mRNA regulatory network, which includes 6 DEcircRNAs, 7 DEmiRNAs, and 45 DEmRNAs. Functional enrichment analysis reveals that these DEmRNAs are mainly involved in immune-related processes. Furthermore, six hub DEmRNAs are identified to establish a hub circRNA regulatory network. Among the DEmRNAs in the network, PRC1 is identified as the most influential node. PRC1 high expression is correlated with poor prognosis and low macrophage infiltration in HCC. Taken together, we identify a certain circRNA regulatory network related to macrophage infiltration and provide novel insight into the mechanism of study and therapeutic targets for HCC.
肿瘤微环境中的免疫细胞在调节肿瘤进展中起着关键作用。肝细胞癌（HCC）中涉及免疫细胞浸润的环状RNA（circRNA）调控网络在很大程度上仍不清楚。在本研究中，使用“估计免疫细胞和癌细胞比例”（EPIC）应用程序从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）评估HCC中免疫细胞、癌症相关成纤维细胞和内皮细胞的比例。巨噬细胞比例高的患者总生存期更好，且巨噬细胞比例是HCC的独立预后因素。接下来，从TCGA和/或GEO数据库中筛选出配对肿瘤组织和非肿瘤组织之间常见的差异表达mRNA（DEmRNAs）、miRNA（DEmiRNAs）和circRNA（DEcircRNAs）。通过Spearman相关性分析，鉴定出与巨噬细胞相关的DEmRNAs，构建了一个circRNA-miRNA-mRNA调控网络，其中包括6个DEcircRNAs、7个DEmiRNAs和45个DEmRNAs。功能富集分析表明，这些DEmRNAs主要参与免疫相关过程。此外，鉴定出六个关键DEmRNAs，建立了一个关键circRNA调控网络。在该网络中的DEmRNAs中，PRC1被确定为最具影响力的节点。PRC1高表达与HCC预后不良和巨噬细胞浸润低相关。综上所述，我们鉴定出了一个与巨噬细胞浸润相关的特定circRNA调控网络，并为HCC的研究机制和治疗靶点提供了新的见解。
