A blood-based epigenetic test for early detection of nasopharyngeal carcinoma (NPC).

Abstract

6063 Background: NPC is highly curable in early stages but 70% of NPC patients are diagnosed with advanced disease due to lack of effective screening. Genetic and epigenetic alterations involved in the pathogenesis of NPC are known. The higher order chromosomal structures reflecting aberrant transcriptional states of these genes can be measured via techniques such as chromosome conformation capture. Detection of these changes in peripheral blood may provide an accurate test for the early cancer detection. Methods: Blood samples have been collected from 84 patients with histologically confirmed NPC and 100 matched controls. Samples from 45 NPC patients and 68 controls have been analyzed. Fourteen genes known to be dysregulated in NPC were investigated. Potential higher order juxtaposition sites in the candidate genes were predicted using pattern recognition software. PCR primer sets were designed around the chosen sites to screen potential markers. Twenty-two markers showing predictability between NPC and control samples were analysed for optimal reproducibility using alternative primer sets. The optimal sets of markers were then tested amongst the complete set of samples. The dataset was processed by re-sampling using the synthetic minority oversampling technique. The overall sample was split into two groups (66% training set and 34% test set) in the classification. Results: Sixteen markers from 7 candidate genes were found to be optimal in differentiating between NPC and control samples in the first 103 samples. Using the multilayer perceptron (MLP) classification, the following results were obtained: Sensitivity 88.9%, 95% CI (79.2% - 98.6%); Specificity 72.7%, 95% CI (58.9% - 86.5%); PPV 72.7%, 95% CI (58.9% - 86.5%); NPV 88.9%, 95% CI (79.2% - 98.6%). The accuracy of the test was similar in detection of stage I and II NPC versus that of stage III or IV NPC. Conclusions: Using a PCR-based method to detect alterations in the cancer epigenome, the feasibility of developing a blood test of potential utility in early diagnosis of NPC was demonstrated. Analysis of larger numbers of patient samples and optimization of markers are ongoing. The performance characteristics of the test in the total population of 184 samples will be presented.