Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma

Abstract

Tumor mutation burdens (TMBs) act as an indicator of immunotherapeutic responsiveness in various tumors. However, the relationship between TMBs and immune cell infiltrates in hepatocellular carcinoma (HCC) is still obscure. The present study aimed to explore the potential diagnostic markers of TMBs for HCC and analyze the role of immune cell infiltration in this pathology. We used OA datasets from The Cancer Genome Atlas database. First, the “maftools” package was used to screen the highest mutation frequency in all samples. R software was used to identify differentially expressed genes (DEGs) according to mutation frequency and perform functional correlation analysis. Then, the gene ontology (GO) enrichment analysis was performed with “clusterProfiler”, “enrichplot”, and “ggplot2” packages. Finally, the correlations between diagnostic markers and infiltrating immune cells were analyzed, and CIBERSORT was used to evaluate the infiltration of immune cells in HCC tissues. As a result, we identified a total of 359 DEGs in this study. These DEGs may affect HCC prognosis by regulating fatty acid metabolism, hypoxia, and the P53 pathway. The top 15 genes were selected as the hub genes through PPI network analysis. SRSF1, SNRPA1, and SRSF3 showed strong similarities in biological effects, NCBP2 was demonstrated as a diagnostic marker of HCC, and high NCBP2 expression was significantly correlated with poor over survival (OS) in HCC. In addition, NCBP2 expression was correlated with the infiltration of B cells (r = 0.364, p = 3.30 × 10−12), CD8+ T cells (r = 0.295, p = 2.71 × 10−8), CD4+ T cells, (r = 0.484, p = 1.37 × 10−21), macrophages (r = 0.551, p = 1.97 × 10−28), neutrophils (r = 0.457, p = 3.26 × 10−19), and dendritic cells (r = 0.453, p = 1.97 × 10−18). Immune cell infiltration analysis revealed that the degree of central memory T-cell (Tcm) infiltration may be correlated with the HCC process. In conclusion, NCBP2 can be used as diagnostic markers of HCC, and immune cell infiltration plays an important role in the occurrence and progression of HCC.

Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma

“…A recently published study identified the NCBP2 gene among the highly mutated genes in high-TMB HCC patients. This gene is involved in the regulation of proliferation, metastasis, and apoptosis, and has been proposed as a novel biomarker of carcinogenesis and cancer progression [ 150 ].…”

Exploration of the role of oxidative stress-related genes in LPS-induced acute lung injury via bioinformatics and experimental studies

“…The clusterProfiler package (version 4.2.2) 38 was used to implement the GO and the Kyoto Encyclopedia of KEGG enrichment of DE-ALI-OSRGs, and the enrichment results were visualized using GOplot (version 1.0.2) 39 and enrichplot packages (version 1.10.2) 40 .…”

Integrated analysis of single‐cell sequencing and weighted co‐expression network identifies a novel signature based on cellular senescence‐related genes to predict prognosis in glioblastoma

“…We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to identify the biological role of the cellular senescence‐related differentially expressed genes (DEGs) using “Clusterprofiler,” “http://org.hs.eg.db,” “ggplot2,” and “enrichplot” R packages between different risk groups 21 …”