Abstract A37: Peripheral blood DNA methylation profiles are predictive of head and neck squamous cell carcinoma

Abstract

Abstract Head and neck cancer accounts for an estimated 47,560 new cases and 11,480 deaths annually in the United States, the majority of which are squamous cell carcinomas (HNSCC). The overall 5-year survival is approximately 60% and declines with increasing stage at diagnosis, indicating a need for non-invasive tests that facilitate the detection of early disease. DNA methylation is a stable epigenetic modification that is amenable to measurement and readily available in peripheral blood. DNA methylation profiles are commonly altered in tumor tissue, including HNSCC. We applied a semi-supervised recursively partitioned mixture model (SS-RPMM) approach to identify novel blood DNA methylation markers of HNSCC using genome-wide methylation array data (26,486 autosomal CpG loci) for peripheral blood samples from 92 HNSCC cases and 92 cancer-free controls. Subjects were randomly split into training (n = 92) and testing (n = 92) sets, stratified by case-control status to ensure an equal distribution of cases and controls between sets. A series of mixed effects models were fit to the training data only and CpG loci were ranked according to absolute t-statistic. The top M loci were selected to train a classifier, where M was chosen using a nested cross-validation procedure, which was then fit to the testing data. To assess the performance of the resultant markers in the testing data, we constructed receiver operating characteristic (ROC) curves and calculated the corresponding area under the curve (AUC). Cases and controls were best differentiated by a methylation profile of 6 CpG loci (associated with FGD4, SERPINF1, WDR39, IL27, HYAL2 and PLEKHA6), resulting in 4 classes, with an AUC of 0.73 (95% CI: 0.62–0.82). After adjustment for subject age, gender, smoking, alcohol consumption and HPV16 serostatus, the AUC increased to 0.85 (95% CI: 0.76–0.92). There was no significant difference in stage at diagnosis, tumor site or HPV-16 serostatus for cases by class. We have identified a novel blood-based methylation profile that is predictive of HNSCC with a high degree of accuracy. Although not yet adequate for use in clinical settings, this profile demonstrates the potential of DNA methylation measured in blood for development of non-invasive applications for detection of head and neck cancer. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A37.