Advertisement

Archives of Gynecology and Obstetrics

, Volume 298, Issue 3, pp 589–596 | Cite as

A prospective study on the predictive value of DNA methylation in cervical intraepithelial neoplasia prognosis

  • Zhengchen Guo
  • Yuanjing Hu
  • Liqin Yuan
  • Na Li
  • Tian Wang
Gynecologic Oncology
  • 59 Downloads

Abstract

Purpose

To study the predictive value of the DNA methylation levels of JAM3, SOX1, SLIT2, C13ORF18, and TERT in the cervical intraepithelial neoplasia prognosis.

Method

In the present study, 139 cases were collected and followed up for 24 months. The DNA methylation levels of JAM3, SOX1, SLIT2, C13ORF18, and TERT were tested from their exfoliated cells. One-way ANOVA, receiver operating characteristic (ROC) curve analyses were conducted to analyze the data.

Results

The DNA methylation of the five genes was associated with prognosis of CIN. The levels of methylation increased as the progression of lesion for the prognosis. For CIN1, difference between DNA methylation of JAM3, SOX1, SLIT2, and C13ORF18 had significance statistically (P < 0.001). Sensitivity (95.2%) and specificity (93.1%) of JAM3 were the highest compared with other genes for the prognosis of CIN1. In addition, for CIN2/3, DNA methylation of JAM3, SOX1, SLIT2, TERT, and C13ORF18 had difference statistically (P < 0.001). JAM3 were also the highest in sensitivity (95.2%) and specificity (93.1%) compared with other genes for the prognosis of CIN2/3.

Conclusions

Our data suggest for the first time that DNA methylation levels are associated with prognosis of CIN significantly. DNA methylation levels of some genes, especially JAM3, may serve as markers for the prediction of the CIN prognosis, including CIN1 nature prognosis and CIN2/3 after treatment.

Keywords

Cervical intraepithelial neoplasia DNA methylation Prognosis JAM3 Follow-up Prospective study 

Notes

Author contributions

ZC Guo: data curation, formal analysis, methodology, and writing original draft. YJ Hu: methodology, supervision, writing review, and editing. LQ Yuan: supervision, data curation, formal analysis, writing review, and editing. N Li: supervision, writing review, and editing. T Wang: writing review and editing.

Funding

This work was supported by Scientific Research Funding of Tianjin Health Bureau (13KG134).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest. Ethical approval this article does not contain any studies with human participants performed by any of the authors.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Kuhn L (2008) Human papillomavirus dna versus papanicolaou screening tests for cervical cancer. N Engl J Med 358(6):642Google Scholar
  2. 2.
    Vasiljevic N, Scibior-Bentkowska D, Brentnall AR, Cuzick J, Lorincz AT (2014) Credentialing of DNA methylation assays for human genes as diagnostic biomarkers of cervical intraepithelial neoplasia in high-risk HPV positive women. Gynecol Oncol 132:709–714CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kristensen LS, Hansen LL (2009) PCR-based methods for detecting single-locus DNA methylation biomarkers in cancer diagnostics, prognostics, and response to treatment. Clin Chem 55:1471–1483CrossRefPubMedGoogle Scholar
  4. 4.
    Yuan L, Hu Y, Zhou Z, Gong Y, Wang R, Li N (2017) Quantitative methylation analysis to detect cervical (pre)-cancerous lesions in high-risk hpv-positive women. Int J Clin Exp Med 10(7):10577–10586Google Scholar
  5. 5.
    Bosch FX, Burchell AN, Schiffman M, Giuliano AR, De SS, Bruni L et al (2008) Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine 26(Suppl 10):K1–K16CrossRefPubMedGoogle Scholar
  6. 6.
    Martin CM, O’Leary JJ (2011) Histology of cervical intraepithelial neoplasia and the role of biomarkers. Best Pract Res Clin Obstet Gynaecol 25(5):605–615CrossRefPubMedGoogle Scholar
  7. 7.
    Katki HA, Gage JC, Schiffman M, Castle PE, Fetterman B, Poitras NE et al (2013) Follow-up testing after colposcopy: five-year risk of cin 2 + after a colposcopic diagnosis of cin 1 or less. J Lower Genit Tract Dis 17(5 Suppl 1):S69CrossRefGoogle Scholar
  8. 8.
    Garrett LA, Mccann CK (2013) Abnormal cytology in 2012: management of atypical squamous cells, low-grade intraepithelial neoplasia, and high-grade intraepithelial neoplasia. Clin Obstet Gynecol 56(1):25–34CrossRefPubMedGoogle Scholar
  9. 9.
    Yoneda JY, Zeferino LC, Marangoni M, Funari MP, Sapper T, Hartman CA et al (2015) Disease recurrence after loop treatment for high grade cervical intraepithelial neoplasia: igcs-0070 cervical cancer. Int J Gynecol Cancer 25 Suppl 1(7):24CrossRefGoogle Scholar
  10. 10.
    Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T et al. (2013) Five-year risk of recurrence after treatment of CIN 2, CIN 3, or AIS: performance of HPV and Pap cotesting in posttreatment management. Doctoral dissertation, Imperial College London (University of London)Google Scholar
  11. 11.
    Eijsink JJ, Lendvai Á, Deregowski V, Klip HG, Verpooten G, Dehaspe L et al (2012) A four-gene methylation marker panel as triage test in high-risk human papillomavirus positive patients. Int J Cancer 130(8):1861CrossRefPubMedGoogle Scholar
  12. 12.
    Hansel A, Steinbach D, Greinke C, Schmitz M, Eiselt J, Scheungraber C et al (2014) A promising dna methylation signature for the triage of high-risk human papillomavirus dna-positive women. PLoS ONE 9(3):e91905CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lim EH, Ng SL, Li JL, Chang AR, Ng J, Ilancheran A et al (2010) Cervical dysplasia: assessing methylation status (methylight) of ccna1, dapk1, hs3st2, pax1 and tfpi2 to improve diagnostic accuracy. Gynecol Oncol 119(2):225CrossRefPubMedGoogle Scholar
  14. 14.
    Ling LI, Jiang W, Zeng SY, Long-Yu LI (2013) Prospective study of hTERC gene detection by fluorescence in situ hybridization in cervical intraepithelial neoplasia 1 natural prognosis. 中国妇产科学术会议 35(3):289–291Google Scholar
  15. 15.
    Huang K, Li LA, Meng Y, You Y, Fu X, Song L (2013) High expression of astrocyte elevated gene-1 (aeg-1) is associated with progression of cervical intraepithelial neoplasia and unfavorable prognosis in cervical cancer. World J Surg Oncol 11(1):297CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Oka N, Kajita M, Nishimura R, Ohbayashi C, Sudo T (2013) L1 gene methylation in high-risk human papillomaviruses for the prognosis of cervical intraepithelial neoplasia. Int J Gynecol Cancer 23(2):235–243CrossRefPubMedGoogle Scholar
  17. 17.
    Uijterwaal MH, Zummeren MV, Kocken M, Luttmer R, Berkhof J, Witte BI et al (2016) Performance of cadm1/mal-methylation analysis for monitoring of women treated for high-grade cin. Gynecol Oncol 143(1):135CrossRefPubMedGoogle Scholar
  18. 18.
    Weber C, Fraemohs L, Dejana E (2007) The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 7:467–477CrossRefPubMedGoogle Scholar
  19. 19.
    Liu Y, Nusrat A, Schnell FJ, Reaves TA, Walsh S, Pochet M, Parkos CA (2000) Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci 113:2363–2374PubMedGoogle Scholar
  20. 20.
    Yin A, Zhang Q, Kong X, Jia L, Yang Z, Meng L, Li L, Wang X, Qiao Y, Lu N, Yang Q, Shen K, Kong B (2015) JAM3 methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix. Oncotarget 6:44373–44387PubMedPubMedCentralGoogle Scholar
  21. 21.
    Clarke MA, Luhn P, Gage JC et al (2017) Discovery and validation of candidate host DNA methylation markers for detection of cervical precancer and cancer. Int J Cancer 141(4):701–710CrossRefPubMedGoogle Scholar
  22. 22.
    Siegel EM, Riggs BM, Delmas AL et al (2015) Quantitative DNA methylation analysis of candidate genes in cervical cancer. PLoS ONE 10(3):e0122495CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Yin A, Zhang Q, Kong X, Lin J, Yang Z, Meng L et al (2015) Jam3 methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix. Oncotarget 6(42):44373–44387CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Tianjin Medical UniversityTianjinChina
  2. 2.Tianjin Central Hospital of Gynecology and ObstetricsTianjinChina

Personalised recommendations