Abstract
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.
Highlights
Primary liver cancer (PLC) is currently the fourth leading cause of cancer-related death and the sixth most common malignant tumor worldwide (Villanueva, 2019)
High Macrophage Fraction Correlates With Good Prognosis for hepatocellular carcinoma (HCC)
The multivariate Cox regression analysis shows that macrophage fraction was the independent prognostic factor for HCC patients in both The Cancer Genome Atlas (TCGA) and GSE14520 data sets (Tables 1, 2)
Summary
Primary liver cancer (PLC) is currently the fourth leading cause of cancer-related death and the sixth most common malignant tumor worldwide (Villanueva, 2019). Hepatocellular carcinoma (HCC) is the predominant form of PLC, accounting for 75–85% of all cases (Bray et al, 2018). Despite advances in diagnosis and curative treatment, the optimal therapeutic methods are still elusive, and the prognosis for HCC remains poor due to late diagnosis.
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