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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus (HCV) infection is a worldwide healthcare problem; however, traditional treatment methods have failed to cure all patients, and HCV has developed resistance to new drugs. Systems biology-based analyses could play an important role in the holistic analysis of the impact of HCV on hepatocellular metabolism. Here, we integrated HCV assembly reactions with a genome-scale hepatocyte metabolic model to identify metabolic targets for HCV assembly and metabolic alterations that occur between different HCV progression states (cirrhosis, dysplastic nodule, and early and advanced hepatocellular carcinoma (HCC)) and healthy liver tissue. We found that diacylglycerolipids were essential for HCV assembly. In addition, the metabolism of keratan sulfate and chondroitin sulfate was significantly changed in the cirrhosis stage, whereas the metabolism of acyl-carnitine was significantly changed in the dysplastic nodule and early HCC stages. Our results explained the role of the upregulated expression of BCAT1, PLOD3 and six other methyltransferase genes involved in carnitine biosynthesis and S-adenosylmethionine metabolism in the early and advanced HCC stages. Moreover, GNPAT and BCAP31 expression was upregulated in the early and advanced HCC stages and could lead to increased acyl-CoA consumption. By integrating our results with copy number variation analyses, we observed that GNPAT, PPOX and five of the methyltransferase genes (ASH1L, METTL13, SMYD2, TARBP1 and SMYD3), which are all located on chromosome 1q, had increased copy numbers in the cancer samples relative to the normal samples. Finally, we confirmed our predictions with the results of metabolomics studies and proposed that inhibiting the identified targets has the potential to provide an effective treatment strategy for HCV-associated liver disorders.
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PMID:Systems biology analysis of hepatitis C virus infection reveals the role of copy number increases in regions of chromosome 1q in hepatocellular carcinoma metabolism. 2704 Jun 43

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Bioinformatics studies have been widely used for screening genes involved in the initiation and progression of HCC. MATERIAL AND METHODS We obtained liver cancer microarray raw data from the GEO database (GSE54238). Next, weighted gene co-expression network analysis (WGCNA) was used to assess the critical modules. Then, we assessed the gene significance by calculating survival, expression level, and receiver operating characteristic (ROC) in the TCGA database. We also validated the expression of selected genes in the Oncomine database and calculated the relationship between 4 hub genes and immune infiltration. Finally, GSEA enrichment analysis was used to explore the potential mechanism. RESULTS We identified the red and blue modules as the critical modules, and found 176 candidate genes by assessing gene significance. GO and KEEG results suggested that the candidate genes are involved in the cell cycle. Four hub genes - SOX4, STK39, TARBP1, and TDRKH - were eventually screened after validating their expression and power in diagnosing HCC in the TCGA database. Immune infiltration analysis and GSEA enrichment analysis showed that these 4 hub genes were correlated with the immune cell populations infiltration and that multiple mechanisms were involved, such as angiogenesis and epithelial-mesenchymal transition. CONCLUSIONS Our findings revealed that these 4 genes can be regarded as potential prognosticators and therapeutic targets for HCC.
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PMID:Identification of Hub Genes in Hepatocellular Carcinoma Related to Progression and Prognosis by Weighted Gene Co-Expression Network Analysis. 3220 Mar 87

The molecular mechanisms underlying hepatocellular carcinoma (HCC) progression remain largely undefined. Here, we identified 176 commonly upregulated genes in HCC tissues based on three Gene Expression Omnibus datasets and The Cancer Genome Atlas (TCGA) cohort. We integrated survival and methylation analyses to further obtain 12 upregulated genes for validation. These genes were overexpressed in HCC tissues at the transcription and protein levels, and increased mRNA levels were related to higher tumor grades and cancer stages. The expression of all markers was negatively associated with overall and disease-free survival in HCC patients. Most of these hub genes can promote HCC proliferation and/or metastasis. These 12 hub genes were also overexpressed and had strong prognostic value in many other cancer types. Methylation and gene copy number analyses indicated that the upregulation of these hub genes was probably due to hypomethylation or increased gene copy numbers. Further, the methylation levels of three genes, KPNA2, MCM3, and LRRC1, were associated with HCC clinical features. Moreover, the levels of most hub genes were related to immune cell infiltration in HCC microenvironments. Finally, we identified three upregulated genes (KPNA2, TARBP1, and RNASEH2A) that could comprehensively and accurately provide diagnostic and prognostic value for HCC patients.
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PMID:Identification of hub genes in hepatocellular carcinoma using integrated bioinformatic analysis. 3221 63