中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 8
Aug.  2019
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Article Contents

Expression of TM6SF2 in hepatocellular carcinoma tissue and its bioinformatics functions

DOI: 10.3969/j.issn.1001-5256.2019.08.017
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  • Received Date: 2019-03-14
  • Published Date: 2019-08-20
  • Objective To investigate the expression of TM6 SF2 in hepatocellular carcinoma (HCC) tissue and its biological functions by data mining in tumor databases. Methods The GEPIA database was applied to measure the change in the mRNA expression level of TM6 SF2 in HCC tissue, and OncoLnc was used to analyze the association of TM6 SF2 expression with the survival time of HCC patients. The cBioPortal and LinkedOmics databases were used to analyze the genes associated with the expression of TM6 SF2 in HCC tissue, and the DAVID6. 8 and STRING databases were used to perform a bioinformatics analysis of TM6 SF2 and the genes associated with its expression. The t-test was used to investigate the difference in the mRNA expression of TM6 SF2 between HCC tissue and adjacent tissue. The Spearman correlation coefficient was used to analyze the correlation of gene expression. The Kaplan-Meier method was used to calculate survival percentage, and the log-rank test was used to analyze the difference in survival percentage. Results Compared with the normal liver tissue, the HCC tissue had low mRNA expression of TM6 SF2 (| log2 FC | cut-off = 0. 5, P < 0. 01) . Compared with those with high expression of TM6 SF2, the patients with low expression had a significant reduction in overall survival time (χ2= 9. 897, P < 0. 01) . Data analysis showed that a total of 49 genes were associated with the expression of TM6 SF2 in HCC tissue, and the gene ontology analysis showed that these genes were enriched in the biological processes and functions including fatty acid synthesis, fatty acid ligase activation, and thrombin regulation (P< 0. 05) . The Kyoto Encyclopedia of Genes and Genome pathway analysis showed that these genes were mainly involved in the signaling pathways of alanine metabolism, peroxisome proliferator-activated receptor signaling pathway, and bile secretion (P < 0. 05) . The protein-protein interaction network analysis showed that the genes of SERPINC1, NR1 I2, SERPINA10, and SLC10 A1 had marked or potential interaction with TM6 SF2 (P < 0. 01) . Conclusion Tumor data mining can quickly obtain the information on the expression of TM6 SF2 in HCC tissue and provide a bioinformatics basis for exploring the role of TM6 SF2 in the development and progression of HCC.

     

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  • [1] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68 (6) :394-424.
    [2] LLOVET JM, ZUCMAN-ROSSI J, PIKARSKY E. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2016, 2:16018.
    [3] LLOVET JM, MONTAL R, SIA D, et al. Molecular therapies and precision medicine for hepatocellular carcinoma[J]. Nat Rev Clin Oncol, 2018, 15 (10) :599-616.
    [4] MAHDESSIAN H, TAXIARCHIS A, POPOV S, et al. TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content[J]. Proc Natl Acad Sci U S A, 2014, 111 (24) :8913-8918.
    [5] KOZLITINA J, SMAGRIS E, STENDER S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease[J]. Nat Genet, 2014, 46 (4) :352-356.
    [6] CHALASANI N, WILSON L, KLEINER DE, et al. Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease[J]. J Hepatol, 2008, 48 (5) :829-834.
    [7] KE RS, ZHANG K, LV LZ, Et al. Prognostic value and oncogene function of heterogeneous nuclear ribonucleoprotein A1overexpression in HBV-related hepatocellular carcinoma[J].Oncol Lett, 2018, 16 (3) :3746-3756.
    [8] ANAYA J. OncoLnc:Linking TCGA survival data to mRNAs, miRNAs, and lncRNAs[J]. Peer J Computer Science, 2016, 2:e67.
    [9] GAO J, AKSOY BA, DOGRUSOZ U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal[J]. Sci Signal, 2013, 6 (269) :pl1.
    [10] VASAIKAR SV, STRAUB P, WANG J, et al. LinkedOmics:Analyzing multi-omics data within and across 32 cancer types[J]. Nucleic Acids Res, 2017, 46 (D1) :d956-d963.
    [11] HUANG DW, SHERMAN BT, LEMPICKI RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J]. Nat Protoc, 2009, 4 (1) :44-57.
    [12] SZKLARCZYK D, FRANCESCHINI A, WYDER S, et al. STRING v10:Protein-protein interaction networks, integrated over the tree of life[J]. Nucleic Acids Res, 2014, 43 (D1) :d447-d452.
    [13] ZHANG YP, WANG F, CHEN PF, et al. Expression and significance of the ABAT gene in hepatocellular carcinoma:An analysis based on data mining[J]. J Clin Hepatol, 2019, 35 (3) :553-558. (in Chinese) 张玉鹏, 王帆, 陈鹏飞, 等.基于数据挖掘分析ABAT基因在肝细胞癌中的表达及意义[J].临床肝胆病杂志, 2019, 35 (3) :553-558.
    [14] ESLAM M, GEORGE J. Genetic and epigenetic mechanisms of NASH[J]. Hepatol Int, 2016, 10 (3) :394-406.
    [15] ESLAM M, VALENTI L, ROMEO S. Genetics and epigenetics of NAFLD and NASH:Clinical impact[J]. J Hepatol, 2018, 68 (2) :268-279.
    [16] ROMEO S, KOZLITINA J, XING C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease[J]. Nat Genet, 2008, 40 (12) :1461-1465.
    [17] DONGIOVANNI P, ROMEO S, VALENTI L. Genetic factors in the pathogenesis of nonalcoholic fatty liver and steatohepatitis[J]. Biomed Res Int, 2015, 2015:460190.
    [18] ANSTEE QM, SETH D, DAY CP. Genetic factors that affect risk of alcoholic and nonalcoholic fatty liver disease[J]. Gastroenterology, 2016, 150 (8) :1728-1744. e7.
    [19] FALLETI E, CUSSIGH A, CMET S, et al. PNPLA3 rs738409and TM6SF2 rs58542926 variants increase the risk of hepatocellular carcinoma in alcoholic cirrhosis[J]. Dig Liver Dis, 2016, 48 (1) :69-75.
    [20] RAKSAYOT M, CHUAYPEN N, KHLAIPHUENGSIN A, et al. Independent and additive effects of PNPLA3 and TM6SF2 polymorphisms on the development of non-B, non-C hepatocellular carcinoma[J]. J Gastroenterol, 2019, 54 (5) :427-436.
    [21] YANG J, TREPO E, NAHON P, et al. PNPLA3 and TM6SF2variants as risk factors of hepatocellular carcinoma across various etiologies and severity of underlying liver diseases[J]. Int J Cancer, 2019, 144 (3) :533-544.
    [22] MELLO T, MATEROZZI M, GALLI A. PPARs and mitochondrial metabolism:From NAFLD to HCC[J]. PPAR Res, 2016, 2016:7403230.
    [23] KIMURA O, KONDO Y, SHIMOSEGAWA T. PPAR could contribute to the pathogenesis of hepatocellular carcinoma[J].PPAR Res, 2012, 2012:574180.
    [24] DAI HH, MEI LQ. Advances in nonalcoholic fatty liver disease and hepatocellular carcinoma research[J]. J Clin Hepatol, 2012, 28 (10) :797-800. (in Chinese) 代鸿华, 梅礼强.非酒精性脂肪性肝病与肝细胞癌关系的研究进展[J].临床肝胆病杂志, 2012, 28 (10) :797-800.
    [25] DIEHL AM, DAY C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis[J]. N Engl J Med, 2017, 377 (21) :2063-2072.
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