IDENTIFICATION OF FREQUENT PROMOTER METHYLATION OF DEATH-ASSOCIATED PROTEIN KINASE IN LIQUID-BASED PAPANICOLAOUS TEST SAMPLES IN VIETNAMESE POPULATION
Keywords:Cervical cancer, Hypermethylation, Methylation-specific-polymerase chain reaction, Death-associated protein kinase, Vietnamese population
Â Objective: The infection of high-risk human papillomavirus (HPV) genotypes, particularly HPV-16 and HPV-18, is known to cause cervical cancer (CC); however, aberrant DNA methylation of death-associated protein kinase (DAPK), a member of tumor suppressor gene family, are required for cervical tumorigenesis. The aim of our study was to evaluate the hypermethylation frequency of CpG belonged to DAPK promoter, in Vietnamese patients, as well as to study about the association between hypermethylation, and high-risk HPV infection leading to CC.
Methods: Methylation-specific-polymerase chain reaction (MSP) was performed to analyze methylation status from 109 liquid-based papanicolaous test samples, collected from local hospital and were identified whether HPV/or non-HPV, high-risk/low-risk HPV infection, then was confirmed by sequencing.
Results: In the case of high-risk HPV infection, the frequency of DAPK gene hypermethylation was 66.67% (24 of 36 cases). Meanwhile, low hypermethylation status was found in low-risk and non-HPV infection, counting for 12.0% (3 of 25 cases), 2.1% (1 of 48 cases), respectively. Significant association of DAPK hypermethylation with high-risk, low-risk, and non-HPV infection was observed (p<0.0001). The DAPK hypermethylation increased the possibility to CC in the case of high-risk HPV infected with high incidence: Odds ratio=34.5 (95% confidence interval [CI]=10.15-117.23, p<0.01), relative risk=12.2 (95% CI=4.56-32.42, p<0.01).
Conclusion: Based on those data, it suggested that MSP carried out on noninvasive samples will lead to potential method to screening, diagnosis and early diagnosis of cervical carcinoma in Vietnamese population.
Kirti, Prabhakar PK. Human papilloma virus associated CC: A review. Asian J Pharm Clin Res 2016;9:14-7.
Malpica A, Matisic JP, Niekirk DV, Crum CP, Staerkel GA, Yamal JM, et al. Kappa statistics to measure inter-rater and intra-rater agreement for 1790 cervical biopsy specimens among twelve pathologists: Qualitative histopathologic analysis and methodologic issues. Gynecol Oncol 2005;993 Suppl 1:S38-52.
Jmaah AK, Malla S, Kumar RS. Cloning and characterization of high risk human papilloma virus (HPV). Asian J Pharm Clin Res 2014;7 Suppl 2:61-5.
Gupta M, Dahiya J, Marwaha RK, Dureja H. Therapies in cancer treatment: An over view. Int J Pharm Pharm Sci 2015;7:1-9.
zur Hausen H. Papillomavirus infections-a major cause of human cancers. Biochim Biophys Acta 1996;1288(2):F55-78.
Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev 2003;16(1):1-17.
Jenkins D. A review of cross-protection against oncogenic HPV by an HPV-16/18 AS04-adjuvanted cervical cancer vaccine: Importance of virological and clinical endpoints and implications for mass vaccination in cervical cancer prevention. Gynecol Oncol 2008;110:S18-25.
Yang HJ. Aberrant DNA methylation in cervical carcinogenesis. Chin J Cancer 2013;32(1):42-8.
Castle PE, Maza M. Prophylactic HPV vaccination: Past, present, and future. Epidemiol Infect 2016;2:1-20.
Vu LT, Bui D, Le HT. Prevalence of cervical infection with HPV type 16 and 18 in Vietnam: Implications for vaccine campaign. BMC Cancer 2013;13:53.
Lazo PA. The molecular genetics of cervical carcinoma. Br J Cancer 1999;80(12):2008-18.
Nath A, Priyanka KK, Anshu AK, Singh CK, Behera S, Singh JK. Hypomethylation of deoxyribonucleic acid in testicular tissue due to arsenic exposure in mice. Asian J Pharm Clin Res 2006;9:294-6.
Sherzay N, Chitakar E. Epigenetics: Effect of environmental factors on human genome. Int J Pharm Pharm Sci 2016;8:1-6.
Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 2001;10(7):687-92.
Lu Q, Ma D, Zhao S. DNA methylation changes in cervical cancers. Methods Mol Biol 2012;863:155-76.
Xiong J, Li Y, Huang K, Lu M, Shi H, Ma L, et al. Association between DAPK1 promoter methylation and cervical cancer: A meta-analysis. PLoS One 2014;9(9):e107272.
Leung RC, Liu SS, Chan KY, Tam KF, Chan KL, Wong LC, et al. Promoter methylation of death-associated protein kinase and its role in irradiation response in cervical cancer. Oncol Rep 2008;19(5):1339-45.
Zhao XL, Meng ZY, Qiao YH, Zhang HL. Promoter methylation of DAPK gene in cervical carcinoma. Ai Zheng 2008;27(9):919-23.
Anjum R, Roux PP, Ballif BA, Gygi SP, Blenis J. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Curr Biol 2005;15(19):1762-7.
Truong PK, Lao TD, Doan TP, Le TA. BRCA1 promoter hypermethylation signature for early detection of breast cancer in the Vietnamese population. Asian Pac J Cancer Prev 2014;15:9607-10.
Truong PK, Lao TD, Doan TP, Le TA. Evaluation of aberrant p16INK4a promoter CpG methylation and its application in Vietnamese breast cancer patients. In: Proceedings of the Fourth International Conference on Advances in Applied Science and Environmental Engineering; 2015. p. 46-50.
Truong PK, Lao TD, Doan TP, Le TA. Loss of expression of cyclin d2 by aberrant DNA methylation: A potential biomarker in vietnamese breast cancer patients. Asian Pac J Cancer Prev 2015;16(6):2209-13.
Whiteside MA, Siegel EM, Unger ER. Human papillomavirus and molecular considerations for cancer risk. Cancer 2008;113 10 Suppl:2981-94.
Leonard SM, Wei W, Collins SI, Pereira M, Diyaf A, Constandinou- Williams C, et al. Oncogenic human papillomavirus imposes an instructive pattern of DNA methylation changes which parallel the natural history of cervical HPV infection in young women. Carcinogenesis 2012;33(7):1286-93.
Burgers WA, Blanchon L, Pradhan S, de Launoit Y, Kouzarides T, Fuks F. Viral oncoproteins target the DNA methyltransferases. Oncogene 2007;26(11):1650-5.
Au Yeung CL, Tsang WP, Tsang TY, Co NN, Yau PL, Kwok TT. HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53. Oncol Rep 2010;24(6):1599-604.
Kahn SL, Ronnett BM, Gravitt PE, Gustafson KS. Quantitative methylation-specific PCR for the detection of aberrant DNA methylation in liquid-based Pap tests. Cancer 2008;114(1):57-64.
Qureshi SA, Bashir MU, Yaqinuddin A. Utility of DNA methylation markers for diagnosing cancer. Int J Surg 2010;8(36):194-8.
Fleischhacker M, Schmidt B. Circulating nucleic acids (CNAs) and cancer - A survey. Biochim Biophys Acta 2007;1775(1):181-232.
Herman JG, Graff JR, MyÃ¶hÃ¤nen S, Nelkin BD, Baylin SB. Methylation-specific PCR: A novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A 1996;93(18):9821-6.
How to Cite
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.