Abstract
Abstract The Department of Defense Serum Repository (DODSR) represents a unique resource enabling longitudinal studies of cancer risk, progression, and response to therapy. The DODSR was initiated in 1989, initially as a means for HIV surveillance, and is comprised of serum samples from active and reserve military personnel drawn at enlistment and annually or biennially throughout the service members' participation in the Military Health System, accompanied by the service member’s electronic health records. This enables the identification of serum samples for all service members with a particular diagnosis, such as Head and Neck Squamous Cell Carcinoma (HNSCC), a cancer significantly represented in the military population with substantial impact on military operations. For HNSCC, 175 cases diagnosed between 2003 and 2013 were identified, as well as 175 corresponding healthy controls matched for age at the time of diagnosis, gender, and ethnicity. Serum samples drawn at the time of diagnosis, 2 and 4 years prior to diagnosis, and 2 years after diagnosis were retrieved and analyzed by targeted mass spectrometry analysis using a panel of 148 qualified selected reaction monitoring (SRM) assays selected from the curated literature and discussions with military oncologists at the Murtha Cancer Center. Initial analyses of 212 samples (38 cases and 38 matched controls, each with 2-4 longitudinal samples) from the total 978 samples available focused on comparisons of pre-diagnosis and at diagnosis serum proteins. Preliminary results identified proteins that were differentially abundant between serum samples taken from HNSCC cases at the time of diagnosis, compared to age-matched controls. Proteins such as A2GL displayed a trend of gradually increasing abundance as a function of time to diagnosis, in HNSC cases, suggesting behavior that may be proven useful for early detection of HNSCC, prior to overt symptoms. These preliminary results suggest that the DODSR can be used to provide serum samples of sufficiently high quality for extensive proteomic analysis, and form cohorts sufficiently large to enable meaningful statistics. Access to longitudinal samples representing years prior to diagnosis enables the identification of serum factors that predict the risk of cancer and may also enable early diagnosis. Access to post-treatment serum samples accompanied with data indicating the clinical response to treatment enables the development of algorithms predicting response to treatment and may eventually contribute to the selection of appropriate therapies. Citation Format: Ju Yeon Lee, Tujin Shi, Vladislav Petyuk, Athena Schepmoes, Thomas Fillmore, Wayne Cardoni, George Coppit, Joseph Goodman, Shiv Srivastava, Craig Shriver, Tao Liu, Karin Rodland. Use of longitudinal samples from the DOD serum repository to identify candidate biomarkers for HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 440.
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