Skip to main content
SpringerLink
Log in

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

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kuhn L (2008) Human papillomavirus dna versus papanicolaou screening tests for cervical cancer. N Engl J Med 358(6):642

    Google Scholar 

  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 132:709–714

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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 55:1471–1483

    Article  PubMed  CAS  Google Scholar 

  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):10577–10586

    Google Scholar 

  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–K16

    Article  PubMed  Google Scholar 

  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):605–615

    Article  PubMed  Google Scholar 

  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):S69

    Article  Google Scholar 

  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):25–34

    Article  PubMed  Google Scholar 

  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):24

    Article  Google Scholar 

  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)

  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):1861

    Article  PubMed  CAS  Google Scholar 

  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):e91905

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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):225

    Article  PubMed  CAS  Google Scholar 

  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):289–291

    Google Scholar 

  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):297

    Article  PubMed  PubMed Central  Google Scholar 

  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):235–243

    Article  PubMed  Google Scholar 

  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):135

    Article  PubMed  CAS  Google Scholar 

  18. Weber C, Fraemohs L, Dejana E (2007) The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 7:467–477

    Article  PubMed  CAS  Google Scholar 

  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 113:2363–2374

    PubMed  CAS  Google Scholar 

  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 6:44373–44387

    PubMed  PubMed Central  Google Scholar 

  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):701–710

    Article  PubMed  CAS  Google Scholar 

  22. Siegel EM, Riggs BM, Delmas AL et al (2015) Quantitative DNA methylation analysis of candidate genes in cervical cancer. PLoS ONE 10(3):e0122495

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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):44373–44387

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

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

Author information

Authors and Affiliations

  1. Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, China

    Zhengchen Guo, Liqin Yuan & Tian Wang

  2. Tianjin Central Hospital of Gynecology and Obstetrics, No. 156, Nankaisan Road, Nankai District, Tianjin, China

    Yuanjing Hu & Na Li

Authors
  1. Zhengchen Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuanjing Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liqin Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Na Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Corresponding author

Correspondence to Yuanjing Hu.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, Z., Hu, Y., Yuan, L. et al. A prospective study on the predictive value of DNA methylation in cervical intraepithelial neoplasia prognosis. Arch Gynecol Obstet 298, 589–596 (2018). https://doi.org/10.1007/s00404-018-4796-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-018-4796-3

Keywords

Search

Navigation