Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma
| Autor: | Peiyong Jiang, Yu K. Tong, Wanxia Gai, Anthony T.C. Chan, Edwin P. Hui, W K Jacky Lam, Brigette B.Y. Ma, Wenlei Peng, Rossa W.K. Chiu, Y.M. Dennis Lo, John K. S. Woo, O Y Olivia Tse, S. H. Cheng, Benny Zee, K.C. Allen Chan, Haiqiang Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Herpesvirus 4 Human Medical Sciences Population Nasopharyngeal neoplasm Biology Cohort Studies 03 medical and health sciences 0302 clinical medicine medicine Carcinoma otorhinolaryngologic diseases Humans Liquid biopsy education Prospective cohort study circulating tumor DNA education.field_of_study Multidisciplinary Massive parallel sequencing Nasopharyngeal Carcinoma liquid biopsy massively parallel sequencing Reproducibility of Results Nasopharyngeal Neoplasms ctDNA Middle Aged Viral Load Biological Sciences medicine.disease Molecular biology stomatognathic diseases 030104 developmental biology Nasopharyngeal carcinoma Molecular Diagnostic Techniques PNAS Plus 030220 oncology & carcinogenesis DNA Viral Female Viral load size-based diagnostics |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 |
| Popis: | Significance We identified differentiating molecular characteristics of plasma EBV DNA between nasopharyngeal carcinoma (NPC) patients and non-NPC subjects. Sequencing-based analysis revealed higher amounts of plasma EBV DNA and generally longer fragment lengths of plasma viral molecules in NPC patients than in non-NPC subjects. Based on these findings, we have developed a highly accurate blood-based test for screening of NPC. Such an approach is shown to enhance the positive predictive value and demonstrate a superior performance for NPC screening. It also obviates the need of a follow-up blood sample and therefore allows single time-point testing. We believe that this more clinically practical protocol would facilitate NPC screening on a population scale. Circulating tumor-derived DNA testing for cancer screening has recently been demonstrated in a prospective study on identification of nasopharyngeal carcinoma (NPC) among 20,174 asymptomatic individuals. Plasma EBV DNA, a marker for NPC, was detected using real-time PCR. While plasma EBV DNA was persistently detectable in 97.1% of the NPCs identified, ∼5% of the general population had transiently detectable plasma EBV DNA. We hypothesized that EBV DNA in plasma of subjects with or without NPC may have different molecular characteristics. We performed target-capture sequencing of plasma EBV DNA and identified differences in the abundance and size profiles of EBV DNA molecules within plasma of NPC and non-NPC subjects. NPC patients had significantly higher amounts of plasma EBV DNA, which showed longer fragment lengths. Cutoff values were established from an exploratory dataset and tested in a validation sample set. Adopting an algorithm that required a sample to concurrently pass cutoffs for EBV DNA counting and size measurements, NPCs were detected at a positive predictive value (PPV) of 19.6%. This represented superior performance compared with the PPV of 11.0% in the prospective screening study, which required participants with an initially detectable plasma EBV DNA result to be retested within 4 weeks. The observed differences in the molecular nature of EBV DNA molecules in plasma of subjects with or without NPC were successfully translated into a sequencing-based test that had a high PPV for NPC screening and achievable through single time-point testing. |
| Databáze: | OpenAIRE |
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