Development of Non-Invasion Method for Prognosis and Early Diagnosis of Cervical Cancer in Vietnamese Patients Based on DNA Methylation Specific PCR

Abstract

Cervical cancer remains one of the common leading cause of cancer death for women worldwide, including Vietnam. Besides the infection of human papilloma virus (HPV) which is the main cause of cervical cancer, increasing evidence demonstrated that inactivation of tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event during carcinogenesis. In current study, aiming to establish biomarker applied in prognosis or early diagnosis for cervical cancer, we developed a powerful assay based on Methylation Specific PCR to detect the aberrant DNA methylation of the panel of cervical cancer related genes in liquid-based Papanicolaou (Pap) tests. Total of 83 liquid-based Pap test samples which were identified whether HPV-infection or non-HPV infection, high-risk HPV oncogenetic type 16 and 18 infection or low-risk HPV infection, were carried by MSP method to evaluate the DNA aberrant methylation occurred in DAPK, RARβ and p16INK4α. According to the results, the hypermethylation reach to 78.8% for RARβ, 63.6% for DAPK and 54.5% for p16INK4α. This hypermethylation characteristic was also associated with HPV high risk genotype infection. Furthermore, the MI values with 97.0% diagnosis coverage, which meant at least one of three genes were methylated. In conclusion, these outcome suggested that the MSP assay carried out on the non-invasive samples (liqid-based pap) will lead to the potential method to prognosis and early diagnosis of cervical carcinoma, as well as allow us to have a vision for these hypermethylation of candidate genes could be a promising biomarker for cervical cancer detection in Vietnamese population.