Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation‐sensitive high resolution melting

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 ear...

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Bibliographic Details
Published in:International journal of cancer 2015-02, Vol.136 (4), p.E127-E135
Main Authors: Yang, Xuesong, Dai, Wei, Kwong, Dora Lai‐wan, Szeto, Carol Y.Y., Wong, Elibe Hiu‐wun, Ng, Wai Tong, Lee, Anne W.M., Ngan, Roger K.C., Yau, Chun Chung, Tung, Stewart Y., Lung, Maria Li
Format: Article
Language:English
Subjects:
Adult
Aged
biomarker
Biomarkers, Tumor - genetics
Biopsy
Cancer
Carcinoma - blood
Carcinoma - diagnosis
Carcinoma - genetics
Case-Control Studies
Cell Line, Tumor
Deoxyribonucleic acid
DNA
DNA Methylation
Early Detection of Cancer
early diagnosis
Epigenesis, Genetic
Epigenetics
Epstein-Barr virus
Female
Genes
Humans
Male
Medical research
Middle Aged
MS‐HRM
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms - blood
Nasopharyngeal Neoplasms - diagnosis
Nasopharyngeal Neoplasms - genetics
Neoplasm Recurrence, Local - diagnosis
Neoplasm Recurrence, Local - genetics
NPC
Promoter Regions, Genetic
ROC Curve
Transition Temperature
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Summary: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. 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.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.29192