Diagnostic Role of Aberrant DNA Promoter Methylation in Ovarian Cancer
Menha Swellam
High Throughput Molecular and Genetic Laboratory, Center for Excellences for Advanced Sciences, National Research Centre, Dokki, Giza, Egypt and Department of Biochemistry, Genetic Engineering and Biotechnology Research Division, National Research Centre, Dokki, Giza, Egypt.
Amal Ramadan *
High Throughput Molecular and Genetic Laboratory, Center for Excellences for Advanced Sciences, National Research Centre, Dokki, Giza, Egypt and Department of Biochemistry, Genetic Engineering and Biotechnology Research Division, National Research Centre, Dokki, Giza, Egypt.
Magda Sayed Mahmoud
High Throughput Molecular and Genetic Laboratory, Center for Excellences for Advanced Sciences, National Research Centre, Dokki, Giza, Egypt and Department of Biochemistry, Genetic Engineering and Biotechnology Research Division, National Research Centre, Dokki, Giza, Egypt.
Maha Hashim
High Throughput Molecular and Genetic Laboratory, Center for Excellences for Advanced Sciences, National Research Centre, Dokki, Giza, Egypt and Department of Biochemistry, Genetic Engineering and Biotechnology Research Division, National Research Centre, Dokki, Giza, Egypt.
Mohamed Emam Sobeih
Department of Medical Oncology, National Cancer Institute, Egypt.
*Author to whom correspondence should be addressed.
Abstract
Background: Alteration of DNA methylation of CpG islands in the promoter regions of tumor suppressor genes is associated with cancer development. We aimed to examine the diagnostic efficacy role of promoter methylated tumor suppressor genes: DAPK, OPCML and DLEC1 in ovarian cancer patients.
Materials and Methods: One hundred forty patients were enrolled (90 with epithelial ovarian cancer [EOC] while the remaining 50 were suffering from benign ovarian lesions. A group of healthy individuals (n=30) were included as control group. Methylation pattern were detected by methylation specific polymerase chain reaction (MSP) in serum samples from all individuals and protein based markers (CEA and CA125) were also estimated.
Results: Promoter methylation was significant for DAPK, OPCML and DLEC1 in EOC as compared to benign ones while all control cases were unmethylated. Significant relation was reported between DAPK, OPCML hypermethylation and FIGO stage, histopathological type and histological grade while DLEC1 hypermethylation was related to both FIGO stage (P= 0.03) and histological grading (P<0.0001). The correlation between promoter hypermethylation with CEA and CA125 showed significant differences. Both sensitivities and specificities for promoter methylation of investigated tumor suppressor genes were superior to CEA and CA125 for early diagnosis of ovarian cancer and detection of early ovarian stages while they were compatible with CA125 in detection of EOC low grades.
Conclusion: Promoter methylation of DAPK, OPCML and DLEC1 genes in circulating blood serves as promising diagnostic approach for early detection of EOC particularly those with early stages, low - grade tumors.
Keywords: Ovarian cancer, DNA methylation, epigenetic changes, diagnosis.