title: Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation-sensitive high resolution melting.
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.
authors.affiliation: Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Dora Lai-wan
authors.initials: DL
authors.lastname: Kwong
authors.forename: Carol Y Y
authors.initials: CY
authors.lastname: Szeto
authors.forename: Elibe Hiu-wun
authors.initials: EH
authors.lastname: Wong
authors.forename: Wai Tong
authors.initials: WT
authors.lastname: Ng
authors.forename: Anne W M
authors.initials: AW
authors.lastname: Lee
authors.forename: Roger K C
authors.initials: RK
authors.lastname: Ngan
authors.forename: Chun Chung
authors.initials: CC
authors.lastname: Yau
authors.forename: Stewart Y
authors.initials: SY
authors.lastname: Tung
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019175:DNA Methylation; D055088:Early Detection of Cancer; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D044366:Transition Temperature
chemical_list: D014408:Biomarkers, Tumor
keywords: DNA methylation; MS-HRM; NPC; biomarker; early diagnosis