Methylation in the promoters of HS3ST2 and CCNA1 genes is associated with cervical cancer in Uygur women in Xinjiang

Int J Biol Markers. 2014 Dec 9;29(4):e354-62. doi: 10.5301/jbm.5000107.

Abstract

We assessed the suitability of HS3ST2 and CCNA1 genes as biomarkers for the early detection of cervical cancer in Uygur women in Xinjiang, China. Methylation-specific PCR (MSP) and HPV (HPV16 and HPV18)-specific PCR were performed on 110 cervical samples: 40 normal cervices, 10 cervical intraepithelial neoplasia 1 (CIN1), 10 CIN2, 10 CIN3 and 40 cervical cancer tissues. The expression of the 2 genes was measured by reverse transcription PCR (RT-PCR) in 10 methylation-positive and 10 methylation-negative cervical tissues. We found that both HS3ST2 and CCNA1 genes were methylated in 38 of the 40 cervical cancer tissues, 9 of the 10 CIN3, and 6 of the 10 CIN2. In contrast, methylation of these 2 genes was found in only 1 of the 40 normal tissues and none of 10 CIN1. Furthermore, hypermethylated HS3ST2 and CCNA1 genes were correlated with infection with HPV16 and HPV18 in high-grade squamous intraepithelial lesions (HSILs) and cervical cancer (both p<0.05). The expression of HS3ST2 and CCNA1 genes was lower in the methylation-positive cervical tissues than in the methylation-negative cervical tissues. Our results indicate that HS3ST2 and CCNA1 genes may play important roles in HPV-induced cervical cancer and that patients with specific hypermethylated genes may have a greater risk of progressing to invasive cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Biomarkers, Tumor / genetics
  • Cervix Uteri / cytology
  • China
  • Cyclin A1 / genetics*
  • DNA Methylation / genetics*
  • Early Detection of Cancer
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 18 / genetics
  • Humans
  • Papillomavirus Infections / genetics
  • Promoter Regions, Genetic / genetics*
  • Sequence Analysis, DNA
  • Squamous Intraepithelial Lesions of the Cervix / genetics
  • Squamous Intraepithelial Lesions of the Cervix / virology
  • Sulfotransferases / genetics*
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / virology

Substances

  • Biomarkers, Tumor
  • CCNA1 protein, human
  • Cyclin A1
  • Sulfotransferases
  • heparitin sulfotransferase