Promoter hypermethylation of tumor suppressor genes in serum as potential biomarker for the diagnosis of nasopharyngeal carcinoma |
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Authors: | Fangyun Tian Shea Ping Yip Dora Lai Wan Kwong Zhixiong Lin Zhining Yang Vincent Wing Cheung Wu |
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Institution: | 1. Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong;2. Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong;3. Cancer Hospital, Shantou University Medical College, Shantou, China |
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Abstract: | Purpose: Promoter hypermethylation of tumor suppressor genes may serve as a promising biomarker for the diagnosis of cancer. Cell-free circulating DNA (cf-DNA) shares hypermethylation status with primary tumors. This study investigated promoter hypermethylation of five tumor suppressor genes as markers in the detection of nasopharyngeal carcinoma (NPC) in serum samples. Methods: cf-DNA was extracted from serum collected from 40 NPC patients and 41 age- and sex-matched healthy subjects. The promoter hypermethylation status of the five genes (RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1) was assessed by methylation-specific PCR after sodium bisulfite conversion. Differences in the methylation status of these five genes between NPC patients and healthy subjects were compared. Results: The concentration of cf-DNA in the serum of NPC patients was significantly higher than that in normal controls. The five tumor suppressor genes – RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1 – were found to be methylated in 17.5%, 22.5%, 25.0%, 51.4% and 64.9% of patients, respectively. The combination of four-gene marker – CDKN2A, DLEC1, DAPK1 and UCHL1 – had the highest sensitivity and specificity in predicting NPC. Conclusion: Screening DNA hypermethylation of tumor suppressor genes in serum was a promising approach for the diagnosis of NPC. |
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Keywords: | DNA hypermethylation Cell-free circulating DNA Tumor suppressor genes MSP Diagnosis Nasopharyngeal carcinoma |
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