中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 36 Issue 6
Jun.  2020
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Article Contents

Value of the NDRG family in the diagnosis and prognostic evaluation of hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2020.06.019
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  • Published Date: 2020-06-20
  • Objective To investigate the expression of the N-myc downstream regulated gene( NDRG) family in hepatocellular carcinoma( HCC) and its association with pathological features and prognosis based on bioinformatics mining. Methods The expression of the NDRG family and the survival data of patients with HCC were obtained using ONCOMINE,GEPIA,and Kaplan-Meier Plotter. The gene expression data of the NDRG family were obtained from 419 HCC tissue samples,which were divided into liver cancer group with 369 samples and normal liver tissue group with 50 samples. Survival data were collected from 364 HCC tissue samples,which were divided into low expression groups( NDRG1 group with 212 samples,NDRG2 group with 185 samples,NDRG3 group with 182 samples,and NDRG4 group with 184 samples) and high expression groups( NDRG1 group with 152 samples,NDRG2 group with 179 samples,NDRG3 group with 182 samples,and NDRG4 group with 180 samples). The t-test was used for comparison of continuous data between two groups,a one-way analysis of variance was used for comparison between multiple groups,and then the Dunnett-t test was performed; the log-rank test were used for survival analysis. Results The expression of NDRG1 and NDRG3 in HCC tissue was higher than that in normal liver tissue,while the expression of NDRG2 in cancer tissue was lower than that in normal liver tissue( all P < 0. 05). There were significant differences in the expression of NDRG1,NDRG2,NDRG3,and NDRG4 between the patients with different pathological stages( F = 3. 67,2. 97,5. 51,and 3. 56,all P<0. 05). The survival analysis showed that compared with the group with low transcription of NDRG1 and NDRG3,the group with high transcription of NDRG1 and NDRG3 had significantly shortened overall survival( OS)( NDRG1: hazard ratio [HR]= 1. 75,95% confidence interval [CI]: 1. 24-2. 47,P < 0. 05; NDRG3: HR = 1. 83,95% CI: 1. 28-2. 60,P < 0. 05) and progression-free survival( PFS)( NDRG1: HR = 1. 39,95% CI: 1. 03-1. 87,P < 0. 05; NDRG3: HR = 1. 71,95% CI: 1. 27-2. 30,P < 0. 05). Compared with the group with low transcription of NDRG2,the group with high transcription of NDRG2 had significantly shortened OS( HR = 0. 43,95% CI:0. 30-0. 62,P < 0. 05) and PFS( HR = 0. 59,95% CI: 0. 44-0. 80,P < 0. 05). There was no significant difference in OS between the group with high transcription of NDRG4 and the group with low transcription of NDRG4( HR = 1. 4,95% CI: 0. 99-1. 98,P >0. 05),and compared with the group with low transcription of NDRG4,the group with high transcription of NDRG4 had significantly prolonged PFS( HR = 0. 53,95% CI: 0. 39-0. 72,P < 0. 05). Conclusion The high expression of NDRG1 and NDRG3 and the low expression of NDRG2 may be associated the progression of HCC and suggest the poor prognosis of HCC patients.

     

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  • [1] TORRE LA,BRAY F,SIEGEL RL,et al. Global cancer statistics,2012[J]. CA Cancer J Clin,2015,65(2):87-108.
    [2] CHEN W,ZHENG R,BAADE PD,et al. Cancer statistics in china,2015[J]. CA Cancer J Clin,2016,66(2):115-132.
    [3] ASKAUTRUD HA,GJERNES E,GUNNES G,et al. Global gene expression analysis reveals a link between NDRG1 and vesicle transport[J]. PLo S One,2014,9(1):e87268.
    [4] PAN H,ZHANG X,JIANG H,et al. Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells[J]. Sci Rep,2017,7:44440.
    [5] LUO Q,WANG CQ,YANG LY,et al. FOXQ1/NDRG1 axis exacerbates hepatocellular carcinoma initiation via enhancing crosstalk between fibroblasts and tumor cells[J]. Cancer Lett,2018,417:21-34.
    [6] JING JS,LI H,WANG SC,et al. NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma[J]. Biosci Rep,2018,38(6):BSR20180907.
    [7] WANG J,YIN D,XIE C,et al. The iron chelator Dp44mT inhibits hepatocellular carcinoma metastasis via N-Myc downstream-regulated gene 2(NDRG2)/gp130/STAT3 pathway[J]. Oncotarget,2014,5(18):8478-8491.
    [8] RHODES DR,YU J,SHANKER K,et al. ONCOMINE:A cancer microarray database and integrated data-mining platform[J].Neoplasia,2004,6(1):1-6.
    [9] TANG Z,LI C,KANG B,et al. GEPIA:A web server for cancer and normal gene expression profiling and interactive analyses[J]. Nucleic Acids Res,2017,45(W1):w98-w102.
    [10] MENYHRT O,NAGY,GYRFFY B. Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma[J]. R Soc Open Sci,2018,5(12):181006.
    [11] CHEN X,CHEUNG ST,SO S,et al. Gene expression patterns in human liver cancers[J]. Mol Biol Cell,2002,13(6):1929-1939.
    [12] WURMBACH E,CHEN YB,KHITROV G,et al. Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma[J]. Hepatology,2007,45(4):938-947.
    [13] LUO EC,CHANG YC,SHER YP,et al. MicroRNA-769-3p down-regulates NDRG1 and enhances apoptosis in MCF-7cells during reoxygenation[J]. Sci Rep,2014,4:5908.
    [14] LI EY,HUANG WY,CHANG YC,et al. Aryl Hydrocarbon receptor activates NDRG1 transcription under hypoxia in breast cancer cells[J]. Sci Rep,2016,6:20808.
    [15] LI Y,PAN P,QIAO P,et al. Downregulation of N-myc downstream regulated gene 1 caused by the methylation of CpG islands of NDRG1 promoter promotes proliferation and invasion of prostate cancer cells[J]. Int J Oncol,2015,47(3):1001-1008.
    [16] WANG PX,YANG X,ZHAO J,et al. The metastasis suppressor,NDRG1,inhibits “stemness” of colorectal cancer via down-regulation of nuclearβ-catenin and CD44[J]. Oncotarget,2015,6(32):33893-33911.
    [17] SONG Y,WU G,ZHANG M,et al. N-myc downstreamregulated gene 1 inhibits the proliferation and invasion of hepatocellular carcinoma cells via the regulation of integrinβ3[J].Oncol Lett,2017,13(5):3599-3607.
    [18] YU C,WU G,DANG N,et al. Inhibition of N-myc downstream-regulated gene 2 in prostatic carcinoma[J]. Cancer Biol Ther,2011,12(4):304-313.
    [19] YIN A,WANG C,SUN J,et al. Overexpression of NDRG2 increases iodine uptake and inhibits thyroid carcinoma cell growth in situ and in vivo[J]. Oncol Res,2016,23(1-2):43-51.
    [20] SHEN L,QU X,LI H,et al. NDRG2 facilitates colorectal cancer differentiation through the regulation of Skp2-p21/p27 axis[J]. Oncogene,2018,37(13):1759-1774.
    [21] CAO W,YU G,LU Q,et al. Low expression of N-myc downstream-regulated gene 2 in oesophageal squamous cell carcinoma correlates with a poor prognosis[J]. BMC Cancer,2013,13:305.
    [22] SONG SP,ZHANG SB,LIU R,et al. NDRG2 down-regulation and CD24 up-regulation promote tumor aggravation and poor survival in patients with gallbladder carcinoma[J]. Med Oncol,2012,29(3):1879-1885.
    [23] LI R,YU C,JIANG F,et al. Overexpression of N-Myc downstream-regulated gene 2(NDRG2)regulates the proliferation and invasion of bladder cancer cells in vitro and in vivo[J].PLo S One,2013,8(10):e76689.
    [24] HUANG J,WU Z,WANG G,et al. N-Myc downstreamregulated gene 2 suppresses the proliferation of T24 human bladder cancer cells via induction of oncosis[J]. Mol Med Rep,2015,12(4):5730-5736.
    [25] WANG J,YIN D,XIE C,et al. The iron chelator Dp44mT inhibits hepatocellular carcinoma metastasis via N-Myc downstream-regulated gene 2(NDRG2)/gp130/STAT3 pathway[J]. Oncotarget,2014,5(18):8478-8491.
    [26] LI B,SHAO Q,JI D,et al. Combined aberrant expression of N-Myc downstream-regulated gene 2 and CD24 is associated with disease-free survival and overal survival in patients with hepatocellular carcinoma[J]. Diagn Pathol,2014,9:209.
    [27] KIM KR,KIM KA,PARK JS,et al. Structural and biophysical analyses of human N-Myc downstream-regulated gene 3(NDRG3)protein[J]. Biomolecules,2020,10(1),90.
    [28] MA J,LIU S,ZHANG W,et al. High expression of NDRG3 associates with positive lymph node metastasis and unfavourable overall survival in laryngeal squamous cell carcinoma[J]. Pathology,2016,48(7):691-696.
    [29] REN GF,TANG L,YANG AQ,et al. Prognostic impact of NDRG2 and NDRG3 in prostate cancer patients undergoing radical prostatectomy[J]. Histol Histopathol,2014,29(4):535-542.
    [30] LUO X,HOU N,CHEN X,et al. High expression of NDRG3associates with unfavorable overall survival in non-small cell lung cancer[J]. Cancer Biomark,2018,21(2):461-469.
    [31] FAN CG,WANG CM,TIAN C,et al. miR-122 inhibits viral replication and cell proliferation in hepatitis B virus-related hepatocellular carcinoma and targets NDRG3[J]. Oncol Rep,2011,26(5):1281-1286.
    [32] JING JS,LI H,WANG SC,et al. NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma[J]. Biosci Rep,2018,38(6):BSR20180907.
    [33] KOTIPATRUNI RP,FERRARO DJ,REN X,et al. NDRG4,the N-Myc downstream regulated gene,is important for cell survival,tumor invasion and angiogenesis in meningiomas[J].Integr Biol(Camb),2012,4(10):1185-1197.
    [34] MELOTTE V,LENTJES MH,VAN DEN BOSCH SM,et al. NMyc downstream-regulated gene 4(NDRG4):A candidate tumor suppressor gene and potential biomarker for colorectal cancer[J]. J Natl Cancer Inst,2009,101(13):916-927.
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