Aberrant methylation status of SPG20 promoter in hepatocellular carcinoma: A potential tumor metastasis biomarker

Cancer Genet. 2019 Apr:233-234:48-55. doi: 10.1016/j.cancergen.2019.04.003. Epub 2019 Apr 12.

Abstract

Purpose: The aim of this study is to analyze the methylation levels of SPG20 promotor region and explore the association between the methylation levels and clinical features in hepatocellular carcinoma (HCC).

Materials and methods: We collected paired of HCC and adjacent non-cancerous tissues (ANT) from 160 HCC patients and analyze the methylation levels through MassARRAY Analyzer 4. The statistical calculations were performed using SPSS version 22.0. Real-time-quantification PCR was performed to assess expression levels of SPG20 in HCC cell lines. Wound healing assay and transwell assay was used to measure cell migration capacity.

Result: We found that mean methylation level of SPG20 in tumor tissues was significantly higher than that in ANT (7.3% vs. 16.2%, P<0.0013). There was a significantly negative correlation between expression level and methylation level of SPG20 (P<0.01). In addition, the methylation levels in HCC were correlated with age and HBV infection. Meanwhile, micro-satellite tumors (P = 0.016) and tumor number (P = 0.018) was found significantly associated with increased methylation levels of several CpG sites and the mean levels of SPG20 promotor in ANT. In addtion, the capacity of cell migration was significantly enhanced in SPG20 knock-down HCC cells.

Conclusion: The hypermethylation status of SPG20 gene promoter is significantly associated with intra-hepatic metastasis and contribute to HCC metastasis.

Keywords: Hepatocellular carcinoma; Metastasis; Methylation; SPG20.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Proteins / genetics*
  • DNA Methylation*
  • Female
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis / genetics*
  • Promoter Regions, Genetic*

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • SPART protein, human