JAM3 methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix

Oncotarget. 2015 Dec 29;6(42):44373-87. doi: 10.18632/oncotarget.6250.

Abstract

DNA methylation is clinically relevant to important tumorigenic mechanisms. This study evaluated the methylation status of candidate genes in cervical neoplasia and determined their diagnostic performance in clinical practice. Cervical cancer and normal cervix tissue was used to select the top 5 discriminating loci among 27 loci in 4 genes (CCNA1, CADM1, DAPK1, JAM3), and one locus of JAM3 (region M4) was identified and confirmed with 267 and 224 cervical scrapings from 2 independent colposcopy referral studies. For patients with atypical squamous cells of unknown significance and those with low-grade squamous intraepithelial lesion, with JAM3-M4 compared to a triage marker of hrHPV testing, the specificity for cervical intraepithelial neoplasia 3 CIN3 and cancer cases (CIN3+) / no neoplasia and CIN1 (CIN1-) was significantly increased, from 21.88 to 81.82 and 15.38 to 85.18, respectively. The corresponding positive predictive value (PPV) was increased from 26.47 to 57.14 and 18.52 to 63.64, respectively. For hrHPV-positive patients, compared to a triage marker of cytology testing, JAM3-M4 showed increased specificity and PPV, from 30.67 to 87.65 and 38.82 to 82.14, respectively. We assessed whether JAM3-M4 could distinguish productive from transforming CIN2; the coincidence rate of JAM3-M4 and P16 was as high as 60.5%.

Keywords: JAM3; cervical neoplasia; complementary; methylation; triage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Atypical Squamous Cells of the Cervix* / chemistry
  • Atypical Squamous Cells of the Cervix* / pathology
  • Atypical Squamous Cells of the Cervix* / virology
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Cell Adhesion Molecules / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • DNA Methylation*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Polymerase Chain Reaction
  • Precancerous Conditions / chemistry
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / pathology
  • Precancerous Conditions / virology
  • Predictive Value of Tests
  • ROC Curve
  • Reproducibility of Results
  • Squamous Intraepithelial Lesions of the Cervix / genetics*
  • Squamous Intraepithelial Lesions of the Cervix / metabolism
  • Squamous Intraepithelial Lesions of the Cervix / pathology
  • Squamous Intraepithelial Lesions of the Cervix / virology
  • Uterine Cervical Dysplasia / chemistry
  • Uterine Cervical Dysplasia / genetics*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / chemistry
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears

Substances

  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • Cyclin-Dependent Kinase Inhibitor p16
  • JAM3 protein, human