中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 3
Mar.  2019
Turn off MathJax
Article Contents

Expression and significance of the ABAT gene in hepatocellular carcinoma:An analysis based on data mining

DOI: 10.3969/j.issn.1001-5256.2019.03.020
Research funding:

 

  • Published Date: 2019-03-20
  • Objective To investigate the expression and significance of the ABAT gene in hepatocellular carcinoma ( HCC) using relateddatabases. Methods The Oncomine database and GEPIA were used to analyze the expression of ABAT in HCC tissue. GEPIA was used toinvestigate the correlation of ABAT mRNA with the survival time and pathological stage of HCC patients. The MethHC database was used toanalyze the methylation level of ABAT promoter region. The String database was used to analyze the network of proteins interacting withABAT protein. The Human Protein Atlas was used to analyze the expression of ABAT protein in HCC tissue and the influence of the proteinexpression of ABAT on prognosis. Results The mRNA expression of ABAT in HCC tissue was significantly lower than that in normal livertissue; patients with lower mRNA expression tended to have a poorer prognosis ( log-rank, P = 0. 002 1) and a higher degree of malignancy ( P = 0. 002 34) . The protein expression of ABAT in HCC tissue was significantly lower than that in normal liver tissue, and patients withlower protein expression tended to have a poorer prognosis ( log-rank, P = 2. 14 × 10-3) . The methylation level of ABAT promoter region inHCC tissue was significantly higher than that in normal liver tissue ( P < 0. 005) . The proteins interacting with ABAT included ALDH1 A3, ALDH9 A1, ALDH3 A2, GAD1, and GAD2, which might be involved in cell functions such as cell apoptosis, redox, and neurotransmittersecretion. Conclusion Data mining of tumor gene databases shows that there are low levels of mRNA and protein expression of ABAT inHCC tissue, which is associated with patient's survival time. At present, database mining can provide a reference for the diagnosis andprognosis evaluation of HCC and a theoretical basis for tumor research in the future.

     

  • loading
  • [1] WALLACE M, PREEN D, JEFFREY G, et al. The evolving epide-miology of hepatocellular carcinoma:A global perspective[J].Expert Rev Gastroenterol Hepatol, 2015, 9 (6) :765-779.
    [2] NAGAPPA M, BINDU PS, CHIPLUNKAR S, et al. Hypersomno-lence-hyperkinetic movement disorder in a child with compoundheterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene[J]. Brain Dev, 2017, 39 (2) :161-165.
    [3] ICHIKAWA K, TSUJI M, TSUYUSAKI Y, et al. Serial magneticresonance imaging and1H-magnetic resonance spectrosco-py in GABA transaminase deficiency:A case report[J]. JIMDRep, 2019, 43:7-12.
    [4] BARNBY G, ABBOTT A, SYKES N, et al. Candidate-genescreening and association analysis at the autism-susceptibilitylocus on chromosome 16p:Evidence of association at GRIN2Aand ABAT[J]. Am J Hum Genet, 2005, 76 (6) :950-966.
    [5] BESSE A, WU P, BRUNI F, et al. The GABA transaminase, ABAT, is essential for mitochondrial nucleoside metabolism[J]. Cell Metabolism, 2015, 21 (3) :417-427.
    [6] BESSE A, PETERSEN AK, HUNTER JV, et al. Personalizedmedicine approach confirms a milder case of ABAT deficiency[J]. Mol Brain, 2016, 9 (1) :93.
    [7] De BIASE D, BARRA D, SIMMACO M, et al. Primary structureand tissue distribution of human 4-aminobutyrate aminotrans-ferase[J]. Eur J Biochem, 1995, 227 (1-2) :476-480.
    [8] BUDCZIES J, BROCKMLLER SF, MLLER BM, et al. Com-parative metabolomics of estrogen receptor positive and estro-gen receptor negative breast cancer:Alterations in glutamineand beta-alanine metabolism[J]. J Proteomics, 2013, 94:279-288.
    [9] CHEN P, WANG F, FENG J, et al. Co-expression network a-nalysis identified six hub genes in association with metastasisrisk and prognosis in hepatocellular carcinoma[J]. Oncotar-get, 2017, 8 (30) :48948-48958.
    [10] REIS H, PADDEN J, AHRENS M, et al. Differential proteomicand tissue expression analyses identify valuable diagnostic bi-omarkers of hepatocellular differentiation and hepatoid adeno-carcinomas[J]. Pathology, 2015, 47 (6) :543-550.
    [11] TANG Z, LI C, KANG B, et al. GEPIA:A web server for cancerand normal gene expression profiling and interactive analyses[J]. Nucleic Acids Res, 2017, 45 (W1) :W98-W102.
    [12] HUANG WY, HSU SD, HUANG HY, et al. Meth HC:A data-base of DNA methylation and gene expression in human canc-er[J]. Nucleic Acids Res, 2015, 43 (Database issue) :d856-d861.
    [13] SZKLARCZYK D, MORRIS JH, COOK H, et al. The STRINGdatabase in 2017:Quality-controlled protein-protein associ-ation networks, made broadly accessible[J]. Nucleic AcidsRes, 2017, 45 (D1) :d362-d368.
    [14] UHLEN M, OKSVOLD P, FAGERBERG L, et al. Towards aknowledge-based human protein atlas[J]. Nat Biotechnol, 2010, 28 (12) :1248-1250.
    [15] UHLEN M, FAGERBERG L, HALLSTROM BM, et al. Proteomics.Tissue-based map of the human proteome[J]. Science, 2015, 347 (6220) :1260419.
    [16] MAS VR, MALUF DG, ARCHER KJ, et al. Genes involved inviral carcinogenesis and tumor initiation in hepatitis C virus-in-duced hepatocellular carcinoma[J]. Mol Med, 2009, 15 (3-4) :85-94.
    [17] ROESSLER S, JIA HL, BUDHU A, et al. A unique metastasisgene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients[J]. Cancer Res, 2010, 70 (24) :10202-10212.
    [18] WURMBACH E, CHEN YB, KHITROV G, et al. Genome-widemolecular profiles of HCV-induced dysplasia and hepatocellularcarcinoma[J]. Hepatology, 2007, 45 (4) :938-947.
    [19] WANG FS, FAN JG, ZHANG Z, et al. The global burden ofliver disease:The major impact of China[J]. Hepatology, 2014, 60 (6) :2099-2108.
    [20] HAN K, KIM JH. Transarterial chemoembolization in hepato-cellular carcinoma treatment:Barcelona clinic liver cancerstaging system[J]. World J Gastroenterol, 2015, 21 (36) :10327-10335.
    [21] CILLO U, VITALE A, GRIGOLETTO F, et al. Prospective vali-dation of the Barcelona clinic liver cancer staging system[J].J Hepatol, 2006, 44 (4) :723-731.
    [22] BUDCZIES J, DENKERT C. Tissue-based metabolomics toanalyze the breast cancer metabolome[J]. Recent ResultsCancer Res, 2016, 207:157-175.
    [23] JANSEN MP, SAS L, SIEUWERTS AM, et al. Decreased ex-pression of ABAT and STC2 hallmarks ER-positive inflamma-tory breast cancer and endocrine therapy resistance in ad-vanced disease[J]. Mol Oncol, 2015, 9 (6) :1218-1233.
    [24] AL-WADEI HA, ULLAH MF, AL-WADEI M. GABA (gamma-aminobutyric acid) , a non-protein amino acid counters thebeta-adrenergic cascade-activated oncogenic signaling inpancreatic cancer:A review of experimental evidence[J].Mol Nutr Food Res, 2011, 55 (12) :1745-1758.
    [25] TIAN H, WU JX, SHAN FX, et al. Gamma-aminobutyric acidinduces tumor cells apoptosis via GABABR1·beta-arrestins·JNKs signaling module[J]. Cell Biochem Biophys, 2015, 71 (2) :679-688.
    [26] INADA T, KOGA M, ISHIGURO H, et al. Pathway-based as-sociation analysis of genome-wide screening data suggestthat genes associated with the gamma-aminobutyric acid re-ceptor signaling pathway are involved in neuroleptic-in-duced, treatment-resistant tardive dyskinesia[J]. Pharma-cogenet Genom, 2008, 18 (4) :317-323.
    [27] LI X, ZHANG J, WU X, et al. Polymorphisms of ABAT, SCN2Aand ALDH5A1 may affect valproic acid responses in the treatmentof epilepsy in Chinese[J]. Pharmacogenomics, 2016, 17 (18) :2007-2014.
    [28] PANOSYAN EH, LIN HJ, KOSTER J, et al. In search of drug-gable targets for GBM amino acid metabolism[J]. BMCCancer, 2017, 17 (1) :162.
    [29] LI C, WANG Q, MA J, et al. Integrative pathway analysis ofgenes and metabolites reveals metabolism abnormal subpath-way regions and modules in esophageal squamous cell carci-noma[J]. Molecules, 2017, 22 (10) :1599.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (1445) PDF downloads(329) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return