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, 19 (2), 1478-1486

Tracking the Important Role of JUNB in Hepatocellular Carcinoma by Single-Cell Sequencing Analysis

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Tracking the Important Role of JUNB in Hepatocellular Carcinoma by Single-Cell Sequencing Analysis

Peng Yan et al. Oncol Lett.

Abstract

Hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer, accounting for ~90% of all primary malignancy of the liver. Although various medical treatments have been used as systemic therapies, patient survival time may be extended by only a few months. Moreover, the underlying mechanisms of HCC development and progression remain poorly understood. In the present study, the single-cell transcriptome of one in vivo HCC tumor sample, two in vitro HCC cell lines and normal peripheral blood mononuclear cells were analysed in order to identify the potential mechanism underlying the development and progression of HCC. Interestingly, JunB proto-oncogene was identified to serve a role in the immune response and in development and progression of HCC, potentially contributing to the development of novel therapeutics for HCC patients.

Keywords: JunB proto-oncogene; hepatocellular carcinoma; immune environment; single-cell RNA-sequencing.

Figures

Figure 1.
Figure 1.
Single-cell transcriptomic data of PBMCs, HCC tumor cells and liver cancer cell lines integration. (A) Integration of PMBC and tumor samples. (B) Identification of cell populations by PCA. (C) Definition of cell types according to the marker genes. (D) Heatmap of the markers identified by PCA. (E) Comparison between expression of marker genes in PBMC and tumor samples. The color blue indicates the expression levels in PBMC samples, the color red in tumor samples. The size of each dot represents the percentage of the cells that expressed the corresponding gene. H1, HuH1; H7, HuH7; Mo, monocytes; NK, natural killer cells; P, epithelial cells; T, T cells; B, B cells; PBMC, peripheral blood mononuclear cells; PCA, principal component analysis; STIM, tumor samples; CTRL, PBMC samples; HCC, hepatocellular carcinoma.
Figure 2.
Figure 2.
Differentially expressed analysis in tumor cells and T cells. (A) A scatter plot of the gene expression correlation between tumor cells and vascular epithelial cells in the peripheral blood. (B) A scatter plot showing the gene expression correlation between T cells infiltrated in the tumor and T cells in the peripheral blood. (C) A heatmap of differentially expressed genes in the comparisons. (D) A Venn diagram of the number of the differential genes with |log2Fold-Change|>2 in the comparisons. (E) Enriched Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways of these differential genes. UMI, unique molecular identifier; PBMC, peripheral blood mononuclear cells.
Figure 3.
Figure 3.
Violin plots of the gene expression levels of JUNB and S100A4 in different cell populations. (A) Gene expression of JUNB in tumor samples. (B) Gene expression of JUNB in PBMC samples. (C) Gene expression of JUNB in integrated samples. (D) Gene expression of S1004A in tumor samples. (E) Gene expression of S1004A in PBMC samples. (F) Gene expression of S1004A in integrated samples. PBMC, peripheral blood mononuclear cells; UMI, unique molecular identifier.
Figure 4.
Figure 4.
Validation of JUNB expression in the TCGA dataset. (A) A scatter plot of the gene expression correlation of APOA2 and JUNB. (B) Mutation and expression level of APOA2 and JUNB in the HCC dataset from TCGA. (C) A Venn diagram of the number of the regulatory elements of APOA2 and JUNB detected in GeneHancer. (D) TFs that coregulated APOA2 and JUNB. Color of the edge indicates the confidence level of the interaction between two proteins. The nodes, in red, indicate the PPAR signaling pathway associated proteins. (E) A survival curve for patients from TCGA with high/low expression of APOA2 and low/high expression of JUNB. TF, transcription factor; TCGA, The Cancer Genome Atlas; APOA2, apolipoprotein A2; PPAR, peroxisome proliferator activated receptor; HCC, hepatocellular carcinoma; JUNB, JunB proto-oncogene.

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