Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation‐sensitive high resolution melting |
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Authors: | Xuesong Yang Wei Dai Dora Lai‐wan Kwong Carol YY Szeto Elibe Hiu‐wun Wong Wai Tong Ng Anne WM Lee Roger KC Ngan Chun Chung Yau Stewart Y Tung Maria Li Lung |
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Institution: | 1. Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China;2. Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China;3. Department of Clinical Oncology, Pamela Youde Nethersole Hospital, Hong Kong Special Administrative Region, People's Republic of China;4. Department of Clinical Oncology, University of Hong Kong‐Shenzhen Hospital, Shenzhen, People's Republic of China;5. Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, People's Republic of China;6. Department of Oncology, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China;7. Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong Special Administrative Region, People's Republic of China |
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Abstract: | Nasopharyngeal carcinoma (NPC) is a human malignancy that is closely associated with Epstein‐Barr Virus (EBV). Early diagnosis of NPC will greatly improve the overall survival. However, current EBV DNA marker detection still lacks the predictive value to perform well in high‐risk populations for early detection of NPC. Since aberrant promoter hypermethylation of tumor suppressor genes (TSGs) is widely considered to be an important epigenetic change in early carcinogenesis, this study identified a panel of methylation markers for early detection of NPC and also assessed the clinical usefulness of these markers with noninvasive plasma specimens instead of biopsies. MS‐HRM assays were carried out to assess the methylation status of a selected panel of four TSGs (RASSF1A, WIF1, DAPK1 and RARβ2) in biopsies, NP brushings and cell‐free plasma from NPC patients. High‐risk and cancer‐free groups were used as controls. DNA methylation panel showed higher sensitivity and specificity than EBV DNA marker in cell‐free plasma from NPC patients at early Stages (I and II) and in addition to the EBV DNA marker, MS‐HRM test for plasma and NP brushing DNA methylation significantly increased the detection rate at all NPC stages as well as local recurrence, using this selected four‐gene panel (p < 0.05). MS‐HRM assay on a selected gene panel has great potential to become a noninvasive and complementary test for NPC early and recurrent detection in combination with the EBV DNA test to increase the sensitivity for NPC detection at an early stage. |
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Keywords: | biomarker DNA methylation NPC MS‐HRM early diagnosis |
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