Background
Hepatocellular carcinoma (HCC) is often caused by chronic liver infection or inflammation. Searching for potential immunotherapy targets will aid the early diagnosis and treatment of HCC.
Methods
Firstly, detailed HCC data were downloaded from The Cancer Genome Atlas database. GDCRNATools was used for the comprehensive analysis of RNA sequencing data. Subsequently, the CIBERSORT package was used to estimate infiltration scores of 22 types of immune cells in complex samples. Furthermore, hub genes were identified via weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis. In addition, multiple databases were used to validate the expression of hub gene in the tumor tissue. Finally, prognostic, diagnostic and immunohistochemical analysis of key hub genes was performed.
Results
In the present study, 9 hub genes were identified using WGCNA and PPI network analysis. Furthermore, the expression levels of 9 genes were positively correlated with the infiltration levels of CD8-positive T (CD8+ T) cells. In multiple dataset validations, the expression levels of CCL5, CXCR6, CD3E, and LCK were decreased in cancer tissues. In addition, survival analysis revealed that patients with LCK low expression had a poor survival prognosis (P < 0.05). Immunohistochemistry results demonstrated that CCL5, CD3E and LCK were expressed at low levels in HCC cancer tissues.
Conclusion
The identification of CCL5, CXCR6, CD3E and LCK may be helpful in the development of early diagnosis and therapy of HCC. LCK may be a potential prognostic biomarker for immunotherapy for HCC.
Background
Nonalcoholic fatty liver disease (NAFLD) as the leading chronic liver disease worldwide causes hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to find potential aberrantly methylated and differentially expressed genes in NAFLD of HCC patients with cirrhosis.
Methods
DNA methylation data, mRNA expression data, and the corresponding clinical information of HCC were downloaded from the Cancer Genome Atlas (TCGA, tissue sample) database. HCC patients with cirrhosis were divided into two groups according to the presence of NAFLD. The differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were obtained.
Results
By overlapping 79 up-regulated genes and 1020 hypomethylated genes, we obtained 5 hypomethylated-highly expressed genes (HypoHGs). By overlapping 365 down-regulated genes and 481 hypermethylated genes, we identified 13 hypermethylated-lowly expressed genes (Hyper-LGs). Survival analysis of these 18 MDEGs indicated that the expression of DGKK and HOXD9 was significantly correlated with the overall survival time of NAFLD patients.
Conclusions
We identified several candidate genes whose expressions were regulated by DNA methylation of NAFLD of HCC with cirrhosis, which may provide a new field in understanding the clinical pathological mechanism of NAFLD of HCC with cirrhosis.
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