Integrative Analysis of Microarray Data to Reveal Regulation Patterns in the Pathogenesis of Hepatocellular Carcinoma
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The integration of multiple profiling data and the construction of a transcriptional regulatory network may provide additional insights into the molecular mechanisms of hepatocellular carcinoma (HCC). The present study was conducted to investigate the deregulation of genes and the transcriptional regulatory network in HCC. Methods: An integrated analysis of HCC gene expression datasets was performed in Gene Expression Omnibus. Functional annotation of the differentially expression genes (DEGs) was conducted. Furthermore, transcription factors (TFs) were identified, and a global transcriptional regulatory network was constructed. Results: An integrated analysis of eight eligible gene expression profiles of HCC led to 1,835 DEGs. Consistent with the fact that the cell cycle is closely related to various tumors, the functional annotation revealed that genes involved in the cell cycle were significantly enriched. A transcriptional regulatory network was constructed using the 62 TFs, which consisted of 872 TF-target interactions between 56 TFs and 672 DEGs in the context of HCC. The top 10 TFs covering the most downstream DEGs were ZNF354C, NFATC2, ARID3A, BRCA1, ZNF263, FOXD1, GATA3, FOXO3, FOXL1, and NR4A2. This network will appeal to future investigators focusing on the development of HCC. Conclusions: The transcriptional regulatory network can provide additional information that is valuable in understanding the underlying molecular mechanism in hepatic tumorigenesis.
Abstract
Background/Aims: The integration of multiple profiling data and the construction of a transcriptional regulatory network may provide additional insights into the molecular mechanisms of hepatocellular carcinoma (HCC). The present study was conducted to investigate the deregulation of genes and the transcriptional regulatory network in HCC. Methods: An integrated analysis of HCC gene expression datasets was performed in Gene Expression Omnibus. Functional annotation of the differentially expression genes (DEGs) was conducted. Furthermore, transcription factors (TFs) were identified, and a global transcriptional regulatory network was constructed. Results: An integrated analysis of eight eligible gene expression profiles of HCC led to 1,835 DEGs. Consistent with the fact that the cell cycle is closely related to various tumors, the functional annotation revealed that genes involved in the cell cycle were significantly enriched. A transcriptional regulatory network was constructed using the 62 TFs, which consisted of 872 TF-target interactions between 56 TFs and 672 DEGs in the context of HCC. The top 10 TFs covering the most downstream DEGs were ZNF354C, NFATC2, ARID3A, BRCA1, ZNF263, FOXD1, GATA3, FOXO3, FOXL1, and NR4A2. This network will appeal to future investigators focusing on the development of HCC. Conclusions: The transcriptional regulatory network can provide additional information that is valuable in understanding the underlying molecular mechanism in hepatic tumorigenesis.
참고문헌 (39)
- Villanueva A, "Liver cancer in 2013. Mutational landscape of HCC: the end of the beginning", Nat Rev Clin Oncol, 11, pp.73~74 (2014)
- El-Serag HB, "Epidemiology of viral hepatitis and hepatocellular carcinoma", Gastroenterology, 142, pp.1264~1273.e1 (2012)
- Stefaniuk P, "Present and future possibilities for early diagnosis of hepatocellular carcinoma", World J Gastroenterol, 16, pp.418~424 (2010)
- Sassa T, "Clinical utility of simultaneous measurement of serum high-sensitivity des-gammacarboxy prothrombin and Lens culinaris agglutinin A-reactive alpha-fetoprotein in patients with small hepatocellular carcinoma", Eur J Gastroenterol Hepatol, 11, pp.1387~1392 (1999)
- Zhu WW, "Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma", Clin Cancer Res, 19, pp.3944~3954 (2013)
- Prieto PA, "DKK1 as a serum biomarker for hepatocellular carcinoma", Hepatobiliary Surg Nutr, 2, pp.127~128 (2013)
- Mao Y, "Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma", Gut, 59, pp.1687~1693 (2010)
- Badr EA, "Role of serum glypican-3 in the diagnosis and differentiation of small hepatocellular carcinoma from hepatitis-C virus cirrhosis", Alexandria J Med, 50, pp.221~226 (2014)
- Stefaniuk P, "Combination of alpha-fetoprotein with gamma-glutamyl transferase as the complementary biomarkers useful in early diagnosis of hepatocellular carcinoma", Exp Clin Hep, 6, pp.40~44 (2010)
- Gan Y, "Diagnostic value of alpha-L-fucosidase for hepatocellular carcinoma: a meta-analysis", Tumour Biol, 35, pp.3953~5960 (2014)
- Yasmin Anum MY, "Combined assessment of TGF-beta-1 and alpha-fetoprotein values improves specificity in the diagnosis of hepatocellular carcinoma and other chronic liver diseases in Malaysia", Med J Malaysia, 64, pp.223~227 (2009)
- Lopez JB, "Recent developments in the first detection of hepatocellular carcinoma", Clin Biochem Rev, 26, pp.65~79 (2005)
- Giannelli G, "SCCA antigen combined with alpha-fetoprotein as serologic markers of HCC", Int J Cancer, 117, pp.506~509 (2005)
- Hafez SS, "Alfa-fetoprotein L3 subfraction and osteopontin: novel markers for the diagnosis of hepatocellular carcinoma", J Am Sci, 9, pp.322~328 (2013)
- Gruden G, "Serum heat shock protein 27levels in patients with hepatocellular carcinoma", Cell Stress Chaperones, 18, pp.235~241 (2013)
- Khattab M, "Role of biomarkers in the prediction and diagnosis of hepatocellular carcinoma", World J Hepatol, 7, pp.2474~2481 (2015)
- Barrett T, "NCBI GEO: archive for functional genomics data sets: update", Nucleic Acids Res, 41(Database issue), pp.D991~D995 (2013)
- Huang DW, "The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists", Genome Biol, 8, pp.R183~ (2007)
- Young MD, "Gene ontology analysis for RNA-seq: accounting for selection bias", Genome Biol, 11, pp.R14~ (2010)
- Kanehisa M, "KEGG: Kyoto encyclopedia of genes and genomes", Nucleic Acids Res, 28, pp.27~30 (2000)
- Knüppel R, "TRANSFAC retrieval program: a network model database of eukaryotic transcription regulating sequences and proteins", J Comput Biol, 1, pp.191~198 (1994)
- Shannon P, "Cytoscape: a software environment for integrated models of biomolecular interaction networks", Genome Res, 13, pp.2498~2504 (2003)
- Sukowati CH, "Significance of hepatitis virus infection in the oncogenic initiation of hepatocellular carcinoma", World J Gastroenterol, 22, pp.1497~1512 (2016)
- Gu Z, "Gene regulation is governed by a core network in hepatocellular carcinoma", BMC Syst Biol, 6, pp.32~ (2012)
- Liang J, "Identification of dysfunctional biological pathways and their synergistic mechanism in hepatocellular carcinoma process", Exp Mol Pathol, 98, pp.540~545 (2015)
- Fu Z, "FOXOs, cancer and regulation of apoptosis", Oncogene, 27, pp.2312~2319 (2008)
- Fei M, "Arsenic trioxide-induced growth arrest of human hepatocellular carcinoma cells involving FOXO3a expression and localization", Med Oncol, 26, pp.178~185 (2009)
- Zhao X, "Threonine 32 (Thr32) of FoxO3 is critical for TGF-β-induced apoptosis via Bim in hepatocarcinoma cells", Protein Cell, 6, pp.127~138 (2015)
- Frietze S, "Genomic targets of the KRAB and SCAN domain-containing zinc finger protein 263", J Biol Chem, 285, pp.1393~1403 (2010)
- Takao M, "Human Nei-like protein NEIL3 has AP lyase activity specific for single-stranded DNA and confers oxidative stress resistance in Escherichia coli mutant", Genes Cells, 14, pp.261~270 (2009)
- Zhang H, "Analysis of loss of heterozygosity on chromosome 4q in hepatocellular carcinoma using highthroughput SNP array", Oncol Rep, 23, pp.445~455 (2010)
- Uhlen M, "Towards a knowledgebased Human Protein Atlas", Nat Biotechnol, 28, pp.1248~1250 (2010)
- Ho DW, "TCGA whole-transcriptome sequencing data reveals significantly dysregulated genes and signaling pathways in hepatocellular carcinoma", Front Med, 9, pp.322~330 (2015)
- Nonaka H, "Serial analysis of gene expression in sinusoidal endothelial cells from normal and injured mouse liver", Biochem Biophys Res Commun, 324, pp.15~24 (2004)
- Yildiz G, "Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis", PLoS One, 8, pp.e64016~ (2013)
- Ueda T, "Gene expression profiling of hepatitis B- and hepatitis C-related hepatocellular carcinoma using graphical Gaussian modeling", Genomics, 101, pp.238~248 (2013)
- Neumann O, "Methylome analysis and integrative profiling of human HCCs identify novel protumorigenic factors", Hepatology, 56, pp.1817~1827 (2012)
- Mah WC, "Methylation profiles reveal distinct subgroup of hepatocellular carcinoma patients with poor prognosis", PLoS One, 9, pp.e104158~ (2014)
- Wang YH, "Plasmalemmal Vesicle Associated Protein (PLVAP) as a therapeutic target for treatment of hepatocellular carcinoma", BMC Cancer, 14, pp.815~ (2014)
