Original Article

Hypermethylation of DcR1 Gene-based Biomarker in Non-invasive Cancer Screening of Vietnamese Cervical Cancer Patients


 Background: The infection of human papillomavirus (HPV) has been considered as the common cause of cervical cancer, which is the leading cause of cancer death in women, in Vietnam. Recently, hypermethylation at tumor suppressor genes (TSGs) has been also demonstrated to be an early epigenetic event and cofactor in human cancer, including cancer of cervix. This study evaluated the frequency of DcR1 gene promoter hypermethylation status as well as whether did or not an association between patterns of DNA hypermethylation and high-risk HPV infection, led to risk of cervical cancer.

Methods: Methylation-Specific-PCR (MSP) was performed to analyze hypermethylation status from 109 liquid-based Papanicolaou test samples, archived and admitted from the Medic Medical Center and Au Lac Clinic Laboratory, Vietnam, from 2011–2014, a kind of non-invasive samples identified whether HPV/or non-HPV, high-risk/low-risk HPV infection.

Results: DcR1 promoter was differentially methylated in 50% cases of high-risk HPV genotype 16 and 18 infected samples. In contrast, a low frequency of hypermethylated DcR1 promoter was found in low risk HPV genotype infected sample (16.0%), and non-HPV infected sample (14.6%). A trend toward positive association was found between hypermethylation of DcR1 gene and HPV exposure was observed (P=0.0005). Moreover, the odds ratio (OR) and relative risk (RR) were found in statistical significant value (OR=5.63 (95%CI = 2.25 - 14.07, P<0.01), RR=3.31 (95%CI = 1.75 - 6.26, P<0.01)).

Conclusion: The hypermethylation of DcR1 gene promoter is a significant characteristic of high-risk HPV infected samples in Vietnamese cervical patients. The OR and RR values showed that the strong correlation between DcR1 hypermethylation and high-risk HPV infection, in which increased the risk of cervical cancer. The combination of DcR1 hypermethylation and HPV detection based biomarker could be used in non-invasive samples obtained from high-risk cancer patients, offer significant practical advantages.




Shivapurkar N, Toyooka S, Toyooka KO et al (2004). Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types. Int J Cancer, 109(5): 786-792.

van Noesel MM, van Bezouw S, Salomons GS et al (2002). Tumor-specific down-regulation of the tumor necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 are associated with dense promoter hypermethylation. Cancer Res, 62(7): 2157-2161.

GLOBOCAN2012:Estimated cancer inci-dence, mortality and prevalence world-wide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx

Burd EM (2003). Human papillomavirus and cervical cancer. Clin Microbiol Rev, 16(1): 1-17.

Castle PE, Maza M (2015). Prophylactic HPV vaccination: past, present, and fu-ture. Epidemiol Infect, 144(3):449-68.

Ingles DJ, Pierce Campbell CM, Messina JA et al. (2015). Human papillomavirus virus (HPV) genotype- and age-specific analyses of external genital lesions among men in the HPV Infection in Men (HIM) Study. J Infect Dis, 211(7): 1060-1067.

Jenkins D (2008). 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, 110: S18-25.

Vu LT, Bui D, Le HT (2013). Prevalence of cervical infection with HPV type 16 and 18 in Vietnam: implications for vaccine campaign. BMC Cancer, 13: 53.

Szalmás A, Kónya J (2009). Epigenetic al-terations in cervical carcinogenesis. Semin Cancer Biol, 19(3): 144-152.

Yang HJ (2013). Aberrant DNA methylation in cervical carcinogenesis. Chin J Cancer, 32(1): 42-48.

Truong KP, Lao DT, Le HAT (2016). Ab-errant DNA Methylation of Adenoma-tous Polyposis Coli Gene with High-Risk Human Papillomavirus in Vietnamese Patients. Springer International Publishing IFMBE Proceedings, Vol. 63, Toi Vo Van et al. (Eds): 6th International Conference on the Development of Biomedical Engineering in Vietnam (BME6), 978-981-10-4360-4, 418946_1_En, (46):521-524.

Truong PK, Lao TD, Le TAH (2017). Evaluation of p16INK4α Hypermethyl-ation from Liquid-based Pap Test Sam-ples in Vietnamese Population. Iran J Public Health, 46(9):1204-1210.

Yoder JA, Walsh CP, Bestor TH (1997). Cytosine methylation and the ecology of intragenomic parasites. Trends Genet, 13(8): 335-340.

Jones PA, Laird PW (1999). Cancer epige-netics comes of age. Nat Genet, 21(2): 163-167.

Widschwendter M, Jones PA (2002). DNA methylation and breast carcinogenesis. Oncogene, 21(35): 5462-5482.

Kahn SL, Ronnett BM, Gravitt PE, Gus-tafson KS (2008). Quantitative methyla-tion-specific PCR for the detection of aberrant DNA methylation in liquid-based Pap tests. Cancer, 114(1): 57-64.

Qureshi SA, Bashir MU, Yaqinuddin A (2010). Utility of DNA methylation markers for diagnosing cancer. Int J Surg, 8(3): 194-198.

Fleischhacker M, Schmidt B (2007). Circu-lating nucleic acids (CNAs) and cancer--a survey. Biochim Biophys Acta, 1775(1): 181-232.

Herman JG, Graff JR, Myöhänen S, Nel-kin BD, Baylin SB (1996). Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A, 93(18): 9821-9826.

Lu Q, Ma D, Zhao S (2012). DNA meth-ylation changes in cervical cancers. Methods Mol Biol, 863: 155-176.

Burgers WA, Blanchon L, Pradhan S, de Launoit Y , Kouzarides T, Fuks F (2007). Viral oncoproteins target the DNA methyltransferases. Oncogene, 26(11): 1650-1655.

Cheng Y, Kim JW, Liu W et al (2009). Genetic and epigenetic inactivation of TNFRSF10C in human prostate cancer. Prostate, 69(3): 327-335.

Michalowski MB, de Fraipont F, Plantaz D, Michelland S, Combaret V, Favrot MC (2008). Methylation of tumor-suppressor genes in neuroblastoma: The RASSF1A gene is almost always methylated in primary tumors. Pediatr Blood Cancer, 50(1): 29-32.

IssueVol 47 No 3 (2018) QRcode
SectionOriginal Article(s)
Cervical cancer DcR1 Hypermethylation MSP Vietnamese population

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How to Cite
TRUONG PK, LAO TD, LE TAH. Hypermethylation of DcR1 Gene-based Biomarker in Non-invasive Cancer Screening of Vietnamese Cervical Cancer Patients. Iran J Public Health. 2018;47(3):350-356.