Abstract
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.
Highlights
Primary liver cancer is one of the most common malignancies, and approximately 80% of primary liver cancers are hepatocellular carcinoma (HCC) [1]
The mRNA-miRNA-long non-coding RNAs (lncRNAs) model was used for the first time to construct a competing endogenous RNA (ceRNA) network in HCC using immune-related mRNAs
Among the MIR4435-2HG/hsa-miR-1-3p/MMP9/hsa-miR-29-3p/DUXAP8 ceRNA network axis components, MMP9 is a member of the matrix metalloproteinase (MMP) family, a class of metal
Summary
Primary liver cancer is one of the most common malignancies, and approximately 80% of primary liver cancers are hepatocellular carcinoma (HCC) [1]. With in-depth research on the mechanism of liver cancer, there has been a great development in the treatment of liver cancer, and the role of tumor immune cells in liver cancer has been well characterized. Tumor immunotherapy is the use of immune principles to activate or strengthen the body’s immune system to remove or inhibit the development of cancer cells in the body [5]. Tumor immunotherapy currently holds good promise for many cancers and has been extensively studied in liver cancer [6]. Immune checkpoint inhibitors, such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies, have been used in the clinic and have shown promising efficacy in patients with advanced liver cancer [7]. Exploring the mechanisms related to immune infiltration can facilitate the development of liver cancer treatment
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