Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia

Infectious Agents and Cancer - Tập 16 - Trang 1-8 - 2021
Claire Bosire1, Adriana C. Vidal2, Jennifer S. Smith3, Dereje Jima4, Zhiqing Huang5, David Skaar4, Fidel Valea6, Rex Bentley7, Margaret Gradison8, Kimberly S. H. Yarnall8, Anne Ford5, Francine Overcash8, Susan K. Murphy5, Cathrine Hoyo4
1Department of Health Behavior, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA
2Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, USA
3Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA
4Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, USA
5Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Duke University School of Medicine, Durham, USA
6Department of Obstetrics and Gynecology, Virginia Tech Carilion School of Medicine, Roanoke, USA
7Department of Pathology, Duke University School of Medicine, Durham, USA
8Department of Family Medicine and Community Health, Duke University School of Medicine, Durham, USA

Tóm tắt

Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited. Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race. Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03–2.36). While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.

Tài liệu tham khảo

American College of Obstetricians and Gynecologists. Practice bulletin no. 168: cervical cancer screening and prevention. Obstet Gynecol. 2016;128(4):e111–e30.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30.

Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2018. Bethesda: National Cancer Institute. 2021. Available at:https://seer.cancer.gov/csr/1975_2018. Accessed May 21 2021.

Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, et al. Screening for cervical cancer: US preventive services task force recommendation statement. JAMA. 2018;320(7):674–86. https://doi.org/10.1001/jama.2018.10897.

Ogilvie GS, van Niekerk D, Krajden M, Smith LW, Cook D, Gondara L, et al. Effect of screening with primary cervical HPV testing vs cytology testing on high-grade cervical intraepithelial neoplasia at 48 months: the HPV FOCAL randomized clinical trial. JAMA. 2018;320(1):43–52. https://doi.org/10.1001/jama.2018.7464.

Koliopoulos G, Nyaga VN, Santesso N, Bryant A, Martin-Hirsch PP, Mustafa RA, et al. Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst Rev. 2017;8:CD008587.

Melnikow J, Henderson JT, Burda BU, Senger CA, Durbin S, Soulsby MA. Screening for cervical cancer with high-risk human papillomavirus testing: a systematic evidence review for the U.S. Prev Serv Task Force. 2018.

Wikström I, Lindell M, Sanner K, Wilander E. Self-sampling and HPV testing or ordinary pap-smear in women not regularly attending screening: a randomised study. Br J Cancer. 2011;105(3):337–9. https://doi.org/10.1038/bjc.2011.236.

Lorincz AT. Cancer diagnostic classifiers based on quantitative DNA methylation. Expert Rev Mol Diagn. 2014;14(3):293–305. https://doi.org/10.1586/14737159.2014.897610.

Kelly H, Benavente Y, Pavon MA, De Sanjose S, Mayaud P, Lorincz AT. Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis. Br J Cancer. 2019;121(11):954–65. https://doi.org/10.1038/s41416-019-0593-4.

Feinberg AP, Koldobskiy MA, Göndör A. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat Rev Genet. 2016;17(5):284–99. https://doi.org/10.1038/nrg.2016.13.

Mai M, Qian C, Yokomizo A, Tindall DJ, Bostwick D, Polychronakos C, et al. Loss of imprinting and allele switching of p73 in renal cell carcinoma. Oncogene. 1998;17(13):1739–41. https://doi.org/10.1038/sj.onc.1202099.

Kazanets A, Shorstova T, Hilmi K, Marques M, Witcher M. Epigenetic silencing of tumor suppressor genes: paradigms, puzzles, and potential. Biochim Biophys Acta. 2016;1865(2):275–88.

Kremer WW, Steenbergen R, Heideman D, Kenter GG, Meijer C. The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review. BJOG. 2021;128(3):504–14. https://doi.org/10.1111/1471-0528.16395.

Nye MD, Hoyo C, Huang Z, Vidal AC, Wang F, Overcash F, et al. Associations between methylation of paternally expressed gene 3 (PEG3), cervical intraepithelial neoplasia and invasive cervical cancer. PLoS One. 2013;8(2):e56325. https://doi.org/10.1371/journal.pone.0056325.

Vidal AC, Henry NM, Murphy SK, Oneko O, Nye M, Bartlett JA, et al. PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer. Clin Transl Oncol. 2014;16(3):266–72. https://doi.org/10.1007/s12094-013-1067-4.

Gomih A, Smith JS, North KE, Hudgens MG, Brewster WR, Huang Z, et al. DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions. Int J Cancer. 2018;143(3):552–60. https://doi.org/10.1002/ijc.31350.

Song JY, Lee JK, Lee NW, Jung HH, Kim SH, Lee KW. Microarray analysis of normal cervix, carcinoma in situ, and invasive cervical cancer: identification of candidate genes in pathogenesis of invasion in cervical cancer. Int J Gynecol Cancer. 2008;18(5):1051–9. https://doi.org/10.1111/j.1525-1438.2007.01164.x.

Zhang J, Yao T, Lin Z, Gao Y. Aberrant methylation of MEG3 functions as a potential plasma-based biomarker for cervical cancer. Sci Rep. 2017;7(1):6271. https://doi.org/10.1038/s41598-017-06502-7.

Rodriguez BA, Weng YI, Liu TM, Zuo T, Hsu PY, Lin CH, et al. Estrogen-mediated epigenetic repression of the imprinted gene cyclin-dependent kinase inhibitor 1C in breast cancer cells. Carcinogenesis. 2011;32(6):812–21. https://doi.org/10.1093/carcin/bgr017.

Nakano S, Murakami K, Meguro M, Soejima H, Higashimoto K, Urano T, et al. Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers. Cancer Sci. 2006;97(11):1147–54. https://doi.org/10.1111/j.1349-7006.2006.00305.x.

Vidal AC, Smith JS, Valea F, Bentley R, Gradison M, Yarnall KS, et al. HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA. Cancer Causes Control. 2014;25(8):1055–62. https://doi.org/10.1007/s10552-014-0406-2.

Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):829–46. https://doi.org/10.1097/AOG.0b013e3182883a34.

Gravitt PE, Peyton CL, Alessi TQ, Wheeler CM, Coutlee F, Hildesheim A, et al. Improved amplification of genital human papillomaviruses. J Clin Microbiol. 2000;38(1):357–61. https://doi.org/10.1128/JCM.38.1.357-361.2000.

Gravitt PE, Peyton CL, Apple RJ, Wheeler CM. Genotyping of 27 human papillomavirus types by using L1 consensus PCR products by a single-hybridization, reverse line blot detection method. J Clin Microbiol. 1998;36(10):3020–7. https://doi.org/10.1128/JCM.36.10.3020-3027.1998.

Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) study group. J Natl Cancer Inst. 1995;87(11):796–802. https://doi.org/10.1093/jnci/87.11.796.

Cogliano V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F. Carcinogenicity of human papillomaviruses. Lancet Oncol. 2005;6(4):204. https://doi.org/10.1016/S1470-2045(05)70086-3.

Apgar BS, Zoschnick L, Wright TC Jr. The 2001 Bethesda system terminology. Am Fam Physician. 2003;68(10):1992–8.

Johnson MD, Wu X, Aithmitti N, Morrison RS. Peg3/Pw1 is a mediator between p53 and Bax in DNA damage-induced neuronal death. J Biol Chem. 2002;277(25):23000–7. https://doi.org/10.1074/jbc.M201907200.

Deng Y, Wu X. Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria. Proc Natl Acad Sci U S A. 2000;97(22):12050–5. https://doi.org/10.1073/pnas.97.22.12050.

Mathur SP, Mathur RS, Gray EA, Lane D, Underwood PG, Kohler M, et al. Serum vascular endothelial growth factor C (VEGF-C) as a specific biomarker for advanced cervical cancer: relationship to insulin-like growth factor II (IGF-II), IGF binding protein 3 (IGF-BP3) and VEGF-A [corrected]. Gynecol Oncol. 2005;98(3):467–83. https://doi.org/10.1016/j.ygyno.2005.05.003.

Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol. 2009;113(1):18–25. https://doi.org/10.1097/AOG.0b013e31818f5008.

Skorstengaard M, Lynge E, Suhr J, Napolitano G. Conservative management of women with cervical intraepithelial neoplasia grade 2 in Denmark: a cohort study. BJOG. 2020;127(6):729-736. https://doi.org/10.1111/1471-0528.16081.

Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al. Benchmarking CIN 3+ risk as the basis for incorporating HPV and pap cotesting into cervical screening and management guidelines. J Low Genit Tract Dis. 2013;17(5 Suppl 1):S28–35. https://doi.org/10.1097/LGT.0b013e318285423c.

Dijkstra MG, Heideman DA, de Roy SC, Rozendaal L, Berkhof J, van Krimpen K, et al. p16(INK4a) immunostaining as an alternative to histology review for reliable grading of cervical intraepithelial lesions. J Clin Pathol. 2010;63(11):972–7. https://doi.org/10.1136/jcp.2010.078634.

Thông tin
Thông tin xuất bản

Infectious Agents and Cancer

Tập 16

1-8

Thông tin tác giả