DNA hypermethylation patterns of APC gene promoter in Vietnamese high-risk HPV infected patients

Truong Kim Phuong; Lao Duc Thuan; Le Huyen Ai Thuy

6 (1) 2016

DNA hypermethylation patterns of APC gene promoter in Vietnamese high-risk HPV infected patients

Author - Affiliation:

Truong Kim Phuong - Ho Chi Minh City Open University , Vietnam

Lao Duc Thuan - Ho Chi Minh City Open University , Vietnam

Le Huyen Ai Thuy - Ho Chi Minh City Open University , Vietnam

Corresponding author: Le Huyen Ai Thuy - thuy.lha@ou.edu.vn

Abstract

Cervical cancer is the leading cause of cancer death in women in Vietnam. Virtually, cervical cancers are associated with infection of HPV (Human papilloma virus). In addition, inactivation of tumor suppressor genes (TSGs), leading by aberrant hypermethylation, an epigenetic mechanism, has been observed in cervical cancer development. Screening for early detection of cervical cancer is importantly increasing from Vietnam, therefore, in current study, we analyzed the aberrant methylation status of APC (Adenomatous polyposis coli) gene, its product has an important role in cell cycle control and maintenance of genomic stability, as the pattern of potential biomarker for cervical cancer in Vietnamese population. The liquid-based Pap test samples which were identified whether HPV-infected or low-risk HPV infected or nonHPV-infected were enrolled and analyzed by MSP (Methylation specific PCR). As the results, the hypermethylation of APC was reached to 75%, 12.5% and 30% in high-risk HPV genotype infected group, in low-risk HPV genotype infected group, and non-HPV genotype infection, respectively. Especially, the characteristic of high-risk HPV infection was also associated with the hypermethylation of candidate gene (p < 0.05). Moreover, the odds ratio and relative risk were found in the high value, counting for 10.5 (95%CI, 2.3 – 47.2) and 3.37 (95%CI, 1.3 – 8.3), respectively. In conclusion, these outcomes suggested that the aberrant hypermethylation of APC gene, which accessed in non-invasive samples, led to the potential biomarker and application in early prognosis and diagnosis to cervical cancer in Vietnamese population.

Keywords

APC gene; cervical cancer; hypermethylation; MSP; Vietnamese population.

Full Text:

PDF

References

Alfonso Dueñas-González, Marcela L, Myrna C, et al. (2005). Epigenetics of cervical cancer. An overview and therapeutic perspectives. Mol Cancer, 4:38.

Aoki K., Taketo MM. (2007). Adenomatous polyposis coli (APC): A multi-functional tumor suppressor gene. Journal of Cell Science, 120(19): 3327-35.

Baylin SB, Esteller M, Rountree MR, et al. (2001). Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet, 10(7):687-92.

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

Castle PE, Maza M. (2015). Prophylactic HPV vaccination: past, present, and future. Epidemiol Infect, 2:1-20.

Chen Y., Zhang C-L., Yong-Zhen L., Yi L, Jing F. (2013). Promoter methylation of APC genes in cervical cancer: correlation with clinicopathologic characteristics. STMOPEN.net.

Esteller M, Corn PG, Baylin SB, et al. (2001). A gene hypermethylation profile of human cancer. Cancer Res, 61(8):3225-9.

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):1060-7.

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.

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

Lu Q, Ma D, Zhao S. (2012). DNA methylation changes in cervical cancers. Methods Mol Biol, 863:155-76.

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

Reesink-Peters N, Wisman GB, Jeronimo C, Tokumaru CY, Cohen Y, Dong SM, et al. (2004) Detecting cervical cancer by quantitative promoter hypermethylation assay on cervical scrapings: a feasibility study. Mol Cancer Res, 2: 289–295.

Schwarzenbach H, Pantel K. (2015). Circulating DNA as biomarker in breast cancer. Breast Cancer Res, 17:136.

Truong PK, Lao TD, Doan TP, Le TA.(2014). BRCA1 promoter hypermethylation signature for early detection of breast cancer in the Vietnamese population. Asian Pac J Cancer Prev, 15(22):9607-10.

Truong PK, Lao TD, Doan TP, Le TA. (2015). Loss of expression of cyclin d2 by aberrant DNA methylation: a potential biomarker in vietnamese breast cancer patients. Asian Pac J Cancer Prev, 16(6):2209-13.

Van der Meide WF, Snellenberg S, Meijer CJ, Baalbergen A, Helmerhorst TJ, van der Sluis WB, et al. (2011) Promoter methylation analysis of WNT/beta-catenin signaling pathway regulators to detect adenocarcinoma or its precursor lesion of the cervix. Gynecol Oncol, 123: 116–122.

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.

Wisman GB, Nijhuis ER, Hoque MO, Reesink-Peters N, Koning AJ, Volders HH, et al. (2006) Assessment of gene promoter hypermethylation for detection of cervical neoplasia. International journal of cancer, 119: 1908–1914.

Yang N, Nijhuis ER, Volders HH, Eijsink JJ, Lendvai A, Zhang B, et al. (2010) Gene promoter methylation patterns throughout the process of cervical carcinogenesis. Cell Oncol, 32: 131–143.

Zarah M., Wingren S., Nilsson T. K. (2011). Hypermethylation of promoter regions of the apc1a and p16ink4a genes in relation to prognosis and tumor characteristics in cervical cancer patients. International journal of oncology, 39: 683-688.

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.