Abstract
Background As the most common hepatic malignancy, hepatocellular carcinoma (HCC) has a high incidence; therefore, in this paper, the immune-related genes were sought as biomarkers in liver cancer. Methods In this study, a differential expression analysis of lncRNA and mRNA in The Cancer Genome Atlas (TCGA) dataset between the HCC group and the normal control group was performed. Enrichment analysis was used to screen immune-related differentially expressed genes. Cox regression analysis and survival analysis were used to determine prognostic genes of HCC, whose expression was detected by molecular experiments. Finally, important immune cells were identified by immune cell infiltration and detected by flow cytometry. Results Compared with the normal group, 1613 differentially expressed mRNAs (DEmRs) and 1237 differentially expressed lncRNAs (DElncRs) were found in HCC. Among them, 143 immune-related DEmRs and 39 immune-related DElncRs were screened out. These genes were mainly related to MAPK cascade, PI3K-AKT signaling pathway, and TGF-beta. Through Cox regression analysis and survival analysis, MMP9, SPP1, HAGLR, LINC02202, and RP11-598F7.3 were finally determined as the potential diagnostic biomarkers for HCC. The gene expression was verified by RT-qPCR and western blot. In addition, CD4 + memory resting T cells and CD8 + T cells were identified as protective factors for overall survival of HCC, and they were found highly expressed in HCC through flow cytometry. Conclusion The study explored the dysregulation mechanism and potential biomarkers of immune-related genes and further identified the influence of immune cells on the prognosis of HCC, providing a theoretical basis for the prognosis prediction and immunotherapy in HCC patients.
Highlights
Hepatocellular carcinoma (HCC), a primary liver cancer in hepatocytes, is a prevalent health problem and one of the most common malignant tumors [1]
Protein-Protein Interaction (PPI) Network. e immune-related differentially expressed mRNAs (DEmRs) were put into Search Tool for the Retrieval of Interacting Genes (STRING) database, whose interaction score > 0.7 was screened to construct a PPI network and visualized using Gephi software. e PPI network was imported into Cytoscape software to identify hub genes of the network by screening the degree of connectivity between genes
By comparing the difference in the tissues from e Cancer Genome Atlas (TCGA) database between the HCC and normal control group, 1613 differentially expressed mRNAs and 1237 differentially expressed Long noncoding RNAs (lncRNAs) (Figures 2(a) and 2(b)) were obtained. 1368 upregulated genes and 245 downregulated genes (Figure 2(c)) were found in DEmRs while 1129 upregulated genes and 108 downregulated genes were found in DElncRs (Figure 2(d))
Summary
As the most common hepatic malignancy, hepatocellular carcinoma (HCC) has a high incidence; in this paper, the immune-related genes were sought as biomarkers in liver cancer. A differential expression analysis of lncRNA and mRNA in e Cancer Genome Atlas (TCGA) dataset between the HCC group and the normal control group was performed. Enrichment analysis was used to screen immune-related differentially expressed genes. Cox regression analysis and survival analysis were used to determine prognostic genes of HCC, whose expression was detected by molecular experiments. Rough Cox regression analysis and survival analysis, MMP9, SPP1, HAGLR, LINC02202, and RP11-598F7.3 were determined as the potential diagnostic biomarkers for HCC. CD4 + memory resting T cells and CD8 + T cells were identified as protective factors for overall survival of HCC, and they were found highly expressed in HCC through flow cytometry. Conclusion. e study explored the dysregulation mechanism and potential biomarkers of immunerelated genes and further identified the influence of immune cells on the prognosis of HCC, providing a theoretical basis for the prognosis prediction and immunotherapy in HCC patients
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