Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation-sensitive high resolution melting
Xuesong Yang
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorWei Dai
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorCorresponding Author
Dora Lai-wan Kwong
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Correspondence to: Maria Li Lung, Room L6-43, 6/F, Laboratory Block, Department of Clinical Oncology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, HKSAR, People's Republic of China, Tel.: +[852-39179783], Fax: +[852-2819-5872], E-mail: [email protected] (or) Dora L. Kwong, Department of Clinical Oncology, University of Hong Kong, 1/F, Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong. HKSAR, People's Republic of China, Tel.: +[852-22554521], Fax: +[852-2872-6426], E-mail: [email protected]Search for more papers by this authorCarol Y.Y. Szeto
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorElibe Hiu-wun Wong
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorWai Tong Ng
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Clinical Oncology, Pamela Youde Nethersole Hospital, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorAnne W.M. Lee
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Clinical Oncology, University of Hong Kong-Shenzhen Hospital, Shenzhen, People's Republic of China
Search for more papers by this authorRoger K.C. Ngan
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorChun Chung Yau
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Oncology, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorStewart Y. Tung
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorCorresponding Author
Maria Li Lung
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Correspondence to: Maria Li Lung, Room L6-43, 6/F, Laboratory Block, Department of Clinical Oncology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, HKSAR, People's Republic of China, Tel.: +[852-39179783], Fax: +[852-2819-5872], E-mail: [email protected] (or) Dora L. Kwong, Department of Clinical Oncology, University of Hong Kong, 1/F, Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong. HKSAR, People's Republic of China, Tel.: +[852-22554521], Fax: +[852-2872-6426], E-mail: [email protected]Search for more papers by this authorXuesong Yang
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorWei Dai
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorCorresponding Author
Dora Lai-wan Kwong
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Correspondence to: Maria Li Lung, Room L6-43, 6/F, Laboratory Block, Department of Clinical Oncology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, HKSAR, People's Republic of China, Tel.: +[852-39179783], Fax: +[852-2819-5872], E-mail: [email protected] (or) Dora L. Kwong, Department of Clinical Oncology, University of Hong Kong, 1/F, Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong. HKSAR, People's Republic of China, Tel.: +[852-22554521], Fax: +[852-2872-6426], E-mail: [email protected]Search for more papers by this authorCarol Y.Y. Szeto
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorElibe Hiu-wun Wong
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorWai Tong Ng
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Clinical Oncology, Pamela Youde Nethersole Hospital, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorAnne W.M. Lee
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Clinical Oncology, University of Hong Kong-Shenzhen Hospital, Shenzhen, People's Republic of China
Search for more papers by this authorRoger K.C. Ngan
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorChun Chung Yau
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Oncology, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorStewart Y. Tung
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong Special Administrative Region, People's Republic of China
Search for more papers by this authorCorresponding Author
Maria Li Lung
Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Correspondence to: Maria Li Lung, Room L6-43, 6/F, Laboratory Block, Department of Clinical Oncology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, HKSAR, People's Republic of China, Tel.: +[852-39179783], Fax: +[852-2819-5872], E-mail: [email protected] (or) Dora L. Kwong, Department of Clinical Oncology, University of Hong Kong, 1/F, Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong. HKSAR, People's Republic of China, Tel.: +[852-22554521], Fax: +[852-2872-6426], E-mail: [email protected]Search for more papers by this authorConflicts of Interest: No potential conflicts of interest were disclosed.
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.
Abstract
What's new?
Tests for Epstein-Barr virus (EBV) DNA may help screen high-risk populations for nasopharyngeal carcinoma (NPC), but these tests are not very sensitive. In this study, the authors developed a panel of biomarkers that instead tests for altered methylation of tumor-suppressor genes. They found that, when plasma and swabs from early-stage NPC patients were analyzed with the methylation panel, it detected the cancer with higher sensitivity and specificity than tests for EBV DNA. Combining the two tests may enhance noninvasive screening for NPC, thus enabling more timely and effective treatments.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
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