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Article Open Access

Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma

  • Authors:
    • Cheng‑Rong Xie
    • Hong‑Guang Sun
    • Yu Sun
    • Wen‑Xiu Zhao
    • Sheng Zhang
    • Xiao‑Min Wang
    • Zhen‑Yu Yin
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, Fujian 361004, P.R. China
    Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 4203-4209
    |
    Published online on: June 22, 2015
       https://doi.org/10.3892/mmr.2015.3970
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Abstract

DLC1 has been shown to be downregulated or absent in hepatocellular carcinoma (HCC) and is associated with tumorigenesis and development. However, only a small number of studies have focused on genetic variations of DLC1. The present study performed exon sequencing for the DLC1 gene in HCC tissue samples from 105 patients to identify functional genetic variation of DLC1 and its association with HCC susceptibility, clinicopathological features and prognosis. A novel missense mutation and four non‑synonymous single nucleotide polymorphisms (SNPs; rs3816748, rs11203495, rs3816747 and rs532841) were identified. A significant correlation of rs3816747 polymorphisms with HCC susceptibility was identified. Compared to individuals with the GG genotype of rs3816747, those with the GA (odds ratio (OR)=0.486; P=0.037) or GA+AA genotype (OR=0.51; P=0.039) were associated with a significantly decreased HCC risk. Furthermore, patients with the GC+CC genotype of rs3816748, the TC+CC genotype of rs11203495 or the GA+AA genotype of rs3816747 had small‑sized tumors compared with those carrying the wild‑type genotype. No significant association of DLC1 SNPs with the patients' prognosis was found. These results indicated that genetic variations in the DLC1 gene may confer a risk for HCC.
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1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Llovet Jm, Bustamante J, Castells A, et al: Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 29:62–67. 1999. View Article : Google Scholar

3 

Cleary Sp, Jeck Wr, Zhao X, et al: Identification of driver genes in hepatocellular carcinoma by exome sequencing. Hepatology. 58:1693–1702. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Huang J, Deng Q, Wang Q, et al: Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma. Nat Genet. 44:1117–1121. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Guichard C, Amaddeo G, Imbeaud S, et al: Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 44:694–698. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS and Popescu NC: Cloning, characterization and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Cancer Res. 58:2196–2199. 1998.PubMed/NCBI

7 

Yamaga M, Kawai K, Kiyota M, Homma Y and Yagisawa H: Recruitment and activation of phospholipase C (PLC)-delta1 in lipid rafts by muscarinic stimulation of PC12 cells: contribution of p122RhoGAP/DLC1, a tumor-suppressing PLCdelta1 binding protein. Adv Enzyme Regul. 48:41–54. 2008. View Article : Google Scholar

8 

Zhou X, Thorgeirsson SS and Popescu NC: Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells. Oncogene. 23:1308–1313. 2004. View Article : Google Scholar

9 

Shih YP, Liao YC, Lin Y and Lo SH: DLC1 negatively regulates angiogenesis in a paracrine fashion. Cancer Res. 70:8270–8275. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Ullmannova V and Popescu NC: Expression profile of the tumor suppressor genes DLC-1 and DLC-2 in solid tumors. Int J Oncol. 29:1127–1132. 2006.PubMed/NCBI

11 

Yuan BZ, Durkin ME and Popescu NC: Promoter hypermeth-ylation of DLC-1, a candidate tumor suppressor gene, in several common human cancers. Cancer Genet Cytogenet. 140:113–117. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Kim TY, Jong HS, Song SH, et al: Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic mechanism in gastric cancer cells. Oncogene. 22:3943–3951. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Au SL, Wong CC, Lee JM, Wong CM and Ng IO: EZH2-mediated H3K27me3 is involved in epigenetic repression of deleted in liver cancer 1 in human cancers. PLoS One. 8:e682262013. View Article : Google Scholar : PubMed/NCBI

14 

Jung SW, Park NH, Shin JW, et al: Prognostic impact of telomere maintenance gene polymorphisms in hepatocellular carcinoma patients with chronic hepatitis B. Hepatology. 59:1912–1920. 2014. View Article : Google Scholar

15 

Dong QZ, Zhang XF, Zhao Y, et al: Osteopontin promoter polymorphisms at locus-443 significantly affect the metastasis and prognosis of human hepatocellular carcinoma. Hepatology. 57:1024–1034. 2013. View Article : Google Scholar

16 

Dong X, Zhou G, Zhai Y, et al: Association of DLC1 gene polymorphism with susceptibility to hepatocellular carcinoma in Chinese hepatitis B virus carriers. Cancer Epidemiol. 33:265–270. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Park SW, Durkin ME, Thorgeirsson SS and Popescu NC: DNA variants of DLC-1, a candidate tumor suppressor gene in human hepatocellular carcinoma. Int J Oncol. 23:133–137. 2003.PubMed/NCBI

18 

Buongiorno P and Bapat B: Rho GTPases and cancer. Prog Mol Subcell Biol. 40:29–53. 2005. View Article : Google Scholar

19 

Gómez del Pulgar T, Benitah SA, Valerón PF, Espina C and Lacal JC: Rho GTPase expression in tumourigenesis: evidence for a significant link. Bioessays. 27:602–613. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Zhou X, Zimonjic DB, Park SW, Yang XY, Durkin ME and Popescu NC: DLC1 suppresses distant dissemination of human hepatocellular carcinoma cells in nude mice through reduction of RhoA GTPase activity, actin cytoskeletal disruption and down-regulation of genes involved in metastasis. Int J Oncol. 32:1285–1291. 2008.PubMed/NCBI

21 

Low JS, Tao Q, Ng KM, et al: A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors. Oncogene. 30:1923–1935. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Ko FC, Yeung YS, Wong CM, et al: Deleted in liver cancer 1 isoforms are distinctly expressed in human tissues, functionally different and under differential transcriptional regulation in hepatocellular carcinoma. Liver Int. 30:139–148. 2010. View Article : Google Scholar

23 

Zhao B, Lu J, Yin J, et al: A functional polymorphism in PER3 gene is associated with prognosis in hepatocellular carcinoma. Liver Int. 32:1451–1459. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Yang Z, Zhou L, Wu LM, Xie HY, Zhang F and Zheng SS: Combination of polymorphisms within the HDAC1 and HDAC3 gene predict tumor recurrence in hepatocellular carcinoma patients that have undergone transplant therapy. Clin Chem Lab Med. 48:1785–1791. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Wong CM, Yam JW, Ching YP, et al: Rho GTPase-activating protein deleted in liver cancer suppresses cell proliferation and invasion in hepatocellular carcinoma. Cancer Res. 65:8861–8868. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Roessler S, Long EL, Budhu A, et al: Integrative genomic identification of genes on 8p associated with hepatocellular carcinoma progression and patient survival. Gastroenterology. 142:957–966. e122012. View Article : Google Scholar :

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Copy and paste a formatted citation
Spandidos Publications style
Xie CR, Sun HG, Sun Y, Zhao WX, Zhang S, Wang XM and Yin ZY: Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma. Mol Med Rep 12: 4203-4209, 2015.
APA
Xie, C., Sun, H., Sun, Y., Zhao, W., Zhang, S., Wang, X., & Yin, Z. (2015). Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma. Molecular Medicine Reports, 12, 4203-4209. https://doi.org/10.3892/mmr.2015.3970
MLA
Xie, C., Sun, H., Sun, Y., Zhao, W., Zhang, S., Wang, X., Yin, Z."Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma". Molecular Medicine Reports 12.3 (2015): 4203-4209.
Chicago
Xie, C., Sun, H., Sun, Y., Zhao, W., Zhang, S., Wang, X., Yin, Z."Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma". Molecular Medicine Reports 12, no. 3 (2015): 4203-4209. https://doi.org/10.3892/mmr.2015.3970
Copy and paste a formatted citation
x
Spandidos Publications style
Xie CR, Sun HG, Sun Y, Zhao WX, Zhang S, Wang XM and Yin ZY: Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma. Mol Med Rep 12: 4203-4209, 2015.
APA
Xie, C., Sun, H., Sun, Y., Zhao, W., Zhang, S., Wang, X., & Yin, Z. (2015). Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma. Molecular Medicine Reports, 12, 4203-4209. https://doi.org/10.3892/mmr.2015.3970
MLA
Xie, C., Sun, H., Sun, Y., Zhao, W., Zhang, S., Wang, X., Yin, Z."Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma". Molecular Medicine Reports 12.3 (2015): 4203-4209.
Chicago
Xie, C., Sun, H., Sun, Y., Zhao, W., Zhang, S., Wang, X., Yin, Z."Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma". Molecular Medicine Reports 12, no. 3 (2015): 4203-4209. https://doi.org/10.3892/mmr.2015.3970
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