Abstract 601: Serological responses to tumor-associated adducts in pancreatic cancer

Abstract

Abstract The incidence of pancreatic cancer has increased over the past several decades and is now the fourth leading cause of cancer death in the USA. Only 8.5% of the patients live beyond 5 years after their initial diagnosis. This dismal survival rate is partly explained by the fact that most pancreatic cancer cases are detected late when treatment options are limited. Novel biomarkers are crucially needed. It has long been recognized that cancer cells abnormally accumulate chemical groups covalently linked to proteins, DNA and other molecules. Humoral responses to these “adducts” have not been thoroughly explored. To investigate these responses, we developed an ELISA platform for the detection of serum IgG reactive to 93 adducts, including post-translational modifications known to contribute to tumorigenesis, progression, and metastasis. Our panel also includes oxidation-related modification, advanced glycation end products, and certain co-enzymes that qualify as adducts based on their binding properties. Using this assay, we measured anti-adduct antibodies in the serum of adult healthy donors (N=24; age range 40-80) as well as patients with pancreatic cancer (N=31; age range 50-90). Importantly, all patient specimens were collected before any treatment. Reactivity to all adducts was analyzed using a random forest predictive model with 10,000 bootstrapped decision trees to distinguish between the two groups. Results revealed a distinctive anti-adduct IgG reactivity profile for pancreatic cancer patients when compared to controls. Applying feature selection using the Boruta algorithm identified a reduced set of 19 target adducts recognized by IgG that most efficiently discriminated between healthy donors and pancreatic cancer cases. All 19 adducts were confirmed as IgG targets in cancer patients using multiple unpaired t-tests (p≤0,05). Aside from their predictive value, we reasoned that the detection of adduct-specific antibodies in cancer patients reflected their accumulation in the tumor cells. To test this hypothesis, we assessed the level of two representative target adducts by immunofluorescence staining in tumor tissue compared to control adjacent non-tumoral tissue or healthy tonsil. Results unequivocally show higher levels of these two adducts in cancer cells compared to non-cancer cells. Taken together, these preliminary findings support our hypothesis of the development of anti-adduct antibodies in pancreatic cancer patients. Furthermore, the specific antibody signature detected in these patients is consistent with the abnormal presence of corresponding adducts in the transformed cells. Our findings pave the way for the development of diagnostic tests based on the detection of serum IgG specific to tumor-associated adducts. Citation Format: Talita Aguiar, Shunya Mashiko, Poulomi Roy, Max Dietzel, Kesava Asam, Bradley Aouizerat, Jeanine Genkinger, Helen Remotti, Emmanuel Zorn. Serological responses to tumor-associated adducts in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 601.