中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 8
Aug.  2021
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(8): 1856-1860

Association of the expression of glucose-6-phosphate dehydrogenase with the prognosis of hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2021.08.021

  • Department of Clinical Laboratory, Center for Gene Diagnosis, Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

Research funding:

National Natural Science Foundation of China (81772276)

  • Received Date: 2020-12-29
  • Accepted Date: 2021-01-25
  • Published Date: 2021-08-20
    Abstract
  •   Objective  To investigate the expression of glucose-6-phosphate dehydrogenase (G6PD) in hepatocellular carcinoma (HCC) tissue and its association with prognosis.  Methods  HCC tissue samples and corresponding adjacent tissue samples were collected from 44 HCC patients who attended Zhongnan Hospital of Wuhan University from June 2016 to January 2018. RT-qRCR was used to measure the mRNA expression of G6PD, and the expression level of G6PD was compared between HCC tissue and adjacent tissue. According to the median of the mRNA expression of G6PD, HCC patients were divided into high G6PD expression group and low G6PD expression group and were analyzed with reference to the data in databases, and the Kaplan-Meier method was used to plot survival curves and investigate the differences in overall survival time and progression-free survival time between the two groups. The t-test was used for comparison of normally distributed continuous data between the two groups, and the Mann-Whitney U test was used for comparison of data with skewed distribution between the two groups; the Fisher's exact test was used for comparison of categorical data between the two groups; the Spearman method was used to perform a correlation analysis.  Results  The mRNA expression level of G6PD in HCC tissue was 2.09 times that in adjacent tissue (Z=-3.221, P=0.001). High expression of G6PD was a risk factor for overall survival time (hazard ratio [HR]=1.84, 95% confidence interval [CI: 1.30-2.61, P=0.000 52) and progression-free survival time (HR=1.75, 95%CI: 1.27-2.42, P=0.000 54) in HCC patients after hepatectomy. The low G6PD expression group had a significantly higher lymphocyte-monocyte ratio (LMR) than the high G6PD expression group (t=2.681, P=0.011), and G6PD was negatively correlated with LMR (r=-0.439, P=0.005).  Conclusion  Elevated expression of G6PD in HCC tissue may lead to a reduction in LMR in HCC patients, suggesting that G6PD expression might be associated with inflammation in tumor microenvironment. High expression of G6PD has a certain clinical value in evaluating the prognosis of HCC.

     

    • FullText(HTML)
  • loading
    • References(26)
  • [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. DOI: 10.3322/caac.21492.
    [2]
    AN L, ZENG HM, ZHENG RS, et al. Liver cancer epidemiology in china, 2015[J]. Chin J Oncol, 2019, 41(10): 721-727. DOI: 10.3760/cma.j.issn.0253?3766.2019.10.001.

    安澜, 曾红梅, 郑荣寿, 等. 2015年中国肝癌流行情况分析[J]. 中华肿瘤杂志, 2019, 41(10): 721-727. DOI: 10.3760/cma.j.issn.0253?3766.2019.10.001.
    [3]
    PATRA KC, HAY N. The pentose phosphate pathway and cancer[J]. Trends Biochem Sci, 2014, 39(8): 347-354. DOI: 10.1016/j.tibs.2014.06.005.
    [4]
    CAI T, KUANG Y, ZHANG C, et al. Glucose-6-phosphate dehydrogenase and NADPH oxidase 4 control STAT3 activity in melanoma cells through a pathway involving reactive oxygen species, c-SRC and SHP2[J]. Am J Cancer Res, 2015, 5(5): 1610-1620. http://europepmc.org/articles/PMC4497430
    [5]
    MELE L, LA NOCE M, PAINO F, et al. Glucose-6-phosphate dehydrogenase blockade potentiates tyrosine kinase inhibitor effect on breast cancer cells through autophagy perturbation[J]. J Exp Clin Cancer Res, 2019, 38(1): 160. DOI: 10.1186/s13046-019-1164-5.
    [6]
    ZHANG R, TAO F, RUAN S, et al. The TGFβ1-FOXM1-HMGA1-TGFβ1 positive feedback loop increases the cisplatin resistance of non-small cell lung cancer by inducing G6PD expression[J]. Am J Transl Res, 2019, 11(11): 6860-6876. http://www.ncbi.nlm.nih.gov/pubmed/31814893
    [7]
    RAO X, DUAN X, MAO W, et al. O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth[J]. Nat Commun, 2015, 6: 8468. DOI: 10.1038/ncomms9468.
    [8]
    BARAJAS JM, REYES R, GUERRERO MJ, et al. The role of miR-122 in the dysregulation of glucose-6-phosphate dehydrogenase (G6PD) expression in hepatocellular cancer[J]. Sci Rep, 2018, 8(1): 9105. DOI: 10.1038/s41598-018-27358-5.
    [9]
    PES GM, ERRIGO A, SORO S, et al. Glucose-6-phosphate dehydrogenase deficiency reduces susceptibility to cancer of endodermal origin[J]. Acta Oncol, 2019, 58(9): 1205-1211. DOI: 10.1080/0284186X.2019.1616815.
    [10]
    ZHANG X, ZHANG X, LI Y, et al. PAK4 regulates G6PD activity by p53 degradation involving colon cancer cell growth[J]. Cell Death Dis, 2017, 8(5): e2820. DOI: 10.1038/cddis.2017.85.
    [11]
    TANG Y, HU HQ, TANG FX, et al. Combined preoperative LMR and CA125 for prognostic assessment of ovarian cancer[J]. J Cancer, 2020, 11(11): 3165-3171. DOI: 10.7150/jca.42477.
    [12]
    MANDALIYA H, JONES M, OLDMEADOW C, et al. Prognostic biomarkers in stage Ⅳ non-small cell lung cancer (NSCLC): Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and advanced lung cancer inflammation index (ALI)[J]. Transl Lung Cancer Res, 2019, 8(6): 886-894. DOI: 10.21037/tlcr.2019.11.16.
    [13]
    ISMAEL MN, FORDE J, MILLA E, et al. Utility of inflammatory markers in predicting hepatocellular carcinoma survival after liver transplantation[J]. Biomed Res Int, 2019, 2019: 7284040. DOI: 10.1155/2019/7284040.
    [14]
    Bureau of Medical Administration, National Health Commission of the People's Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)[J]. J Clin Hepatol, 2020, 36(2): 277-292. DOI: 10.3969/j.issn.1001-5256.2020.02.007.

    中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 临床肝胆病杂志, 2020, 36(2): 277-292. DOI: 10.3969/j.issn.1001-5256.2020.02.007.
    [15]
    European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma[J]. J Hepatol, 2018, 69(1): 182-236. DOI: 10.1016/j.jhep.2018.03.019.
    [16]
    SHANG RZ, QU SB, WANG DS. Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects[J]. World J Gastroenterol, 2016, 22(45): 9933-9943. DOI: 10.3748/wjg.v22.i45.9933.
    [17]
    ZUCMAN-ROSSI J, VILLANUEVA A, NAULT JC, et al. Genetic landscape and biomarkers of hepatocellular carcinoma[J]. Gastroenterology, 2015, 149(5): 1226-1239. e4. DOI: 10.1053/j.gastro.2015.05.061.
    [18]
    LU M, LU L, DONG Q, et al. Elevated G6PD expression contributes to migration and invasion of hepatocellular carcinoma cells by inducing epithelial-mesenchymal transition[J]. Acta Biochim Biophys Sin (Shanghai), 2018, 50(4): 370-380. DOI: 10.1093/abbs/gmy009.
    [19]
    SOSA V, MOLINÉ T, SOMOZA R, et al. Oxidative stress and cancer: An overview[J]. Ageing Res Rev, 2013, 12(1): 376-390. DOI: 10.1016/j.arr.2012.10.004.
    [20]
    MOLONEY JN, COTTER TG. ROS signalling in the biology of cancer[J]. Semin Cell Dev Biol, 2018, 80: 50-64. DOI: 10.1016/j.semcdb.2017.05.023.
    [21]
    YAN YC, WEN K, MAO K, et al. Pathogenesis of hepatitis B virus－related hepatocellular carcinoma[J]. J Clin Hepatol, 2020, 36(10): 2167-2172. DOI: 10.3969/j.issn.1001-5256.2020.10.002.

    颜永聪, 温凯, 毛凯, 等. HBV相关肝细胞癌的发生机制[J]. 临床肝胆病杂志, 2020, 36(10): 2167-2172. DOI: 10.3969/j.issn.1001-5256.2020.10.002.
    [22]
    LIU B, FANG M, HE Z, et al. Hepatitis B virus stimulates G6PD expression through HBx-mediated Nrf2 activation[J]. Cell Death Dis, 2015, 6: e1980. DOI: 10.1038/cddis.2015.322.
    [23]
    LIM CJ, LEE YH, PAN L, et al. Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma[J]. Gut, 2019, 68(5): 916-927. DOI: 10.1136/gutjnl-2018-316510.
    [24]
    CHEN XQ, XUE CR, HOU P, et al. Lymphocyte-to-monocyte ratio effectively predicts survival outcome of patients with obstructive colorectal cancer[J]. World J Gastroenterol, 2019, 25(33): 4970-4984. DOI: 10.3748/wjg.v25.i33.4970.
    [25]
    ZHU YW, YAO MJ, BO YC, et al. Prognostic assessment of lymphocyte-to-monocyte ratio for patients with primary liver cancer after curative hepatectomy[J]. J Zhengzhou Univ (Medical Sciences), 2017, 52(2): 197-200. DOI: 10.13705/j.issn.1671-6825.2017.02.023.

    朱艺伟, 姚明解, 薄亚聪, 等. 淋巴细胞与单核细胞比值对原发性肝癌患者根治性切除术后预后的预测价值[J]. 郑州大学学报(医学版), 2017, 52(2): 197-200. DOI: 10.13705/j.issn.1671-6825.2017.02.023.
    [26]
    MANO Y, YOSHIZUMI T, YUGAWA K, et al. Lymphocyte-to-monocyte ratio is a predictor of survival after liver transplantation for hepatocellular carcinoma[J]. Liver Transpl, 2018, 24(11): 1603-1611. DOI: 10.1002/lt.25204.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 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

    Figures(2)  / Tables(2)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (711) PDF downloads(59) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return