Identification of Key Functional Modules and Immunomodulatory Regulators of Hepatocellular Carcinoma

Abstract

Despite the advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfactory due to postsurgical recurrence and treatment resistance. Therefore, it is important to reveal the mechanisms underlying HCC and identify potential therapeutic targets against HCC, which could facilitate the development of novel therapies. Based on 12 HCC samples and 12 paired paracancerous normal tissues, we identified differentially expressed mRNAs and lncRNAs using the “limma” package in R software. Moreover, we used the weighted gene coexpression network analysis (WGCNA) to analyze the expression data and screened hub genes. Furthermore, we performed pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In addition, the relative abundance of a given gene set was estimated by single-sample Gene Set Enrichment Analysis. We identified 687 differentially expressed mRNAs and 260 differentially expressed lncRNAs. A total of 6 modules were revealed by WGCNA, and MT1M and MT1E genes from the red module were identified as hub genes. Moreover, pathway analysis revealed the top 10 enriched KEGG pathways of upregulated or downregulated genes. Additionally, we also found that CD58 might act as an immune checkpoint gene in HCC via PD1/CTLA4 pathways and regulate the levels of tumor-infiltrating immune cells in HCC tissues, which might be an immunotherapeutic target in HCC. Our research identified key functional modules and immunomodulatory regulators for HCC, which might offer novel diagnostic biomarkers and/or therapeutic targets for cancer immunotherapy.

Combining single-cell and bulk RNA sequencing, NK cell marker genes reveal a prognostic and immune status in pancreatic ductal adenocarcinoma

“…However, there are few studies on ASCL2 in PDAC. Previous studies suggested that these NK cell marker genes involve immune regulatory processes (For example, NINL and KDM6B in gastric cancer 72 , 73 , PLAAT4 in pancreatic carcinoma 59 , SKIL in non-small cell lung cancer 74 , MT1E in liver cancer 75 , ASCL2 in colorectal cancer) 76 in solid malignant tumors. The identification of NKCMGS of PDAC provides a potential target for therapeutic and mechanistic studies of PDAC.…”

RNA-Seq and Immune Repertoire Analysis of Normal and Hepatocellular Carcinoma Relapse After Liver Transplantation

“… 26 Previous studies have also revealed a key role for immune cells in the initiation, metastasis, and recurrence of HCC. 27 , 28 Therefore, it is necessary to reveal the potential mechanism of HCC relapse and identify potential predictive targets, with emphasis on immune repertoire profiling. Based on the RNA-seq data, a differential analysis of immune cells in the normal and relapse groups was conducted, and it was found that there were significant differences in the abundance of the five types of immune cells between the two groups.…”

CD58 acts as a tumor promotor in hepatocellular carcinoma via activating the AKT/GSK-3β/β-catenin pathway

“…However, CD58 has recently been shown to be greatly increased in some solid tumors, such as gastric and colorectal malignancies, and malignant gliomas [15][16][17]. A recent study reported that CD58 was overexpressed in HCC tissues and positively correlated with tumor-infiltrating immune cells [18]. However, the function and potential mechanisms of CD58 on HCC remained largely elusive.…”