Abstract P076: Contribution of the microbiome to a metabolomic signature predictive of risk for pancreatic cancer

Abstract Purpose: Emerging evidence implicates the microbiome in the development of pancreatic cancer. We investigated whether increased levels of microbial-related metabolites in circulation are associated with pancreatic cancer risk. Methods: We applied metabolomics profiling to sera from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cohort to quantify and build a model based on 14 microbial-related metabolites. The study involved samples collected from 172 subjects within five years prior to diagnosis and 863 matched controls. Data from five PLCO centers were used for training and from two centers for validation and model selection. The model was subsequently tested using samples from three independent centers. The contributions of non-microbial-associated metabolites as well as CA19-9 was also assessed. Results: A 3-marker microbial-related metabolite panel yielded in the PLCO testing set an AUC of 0.64 (95% CI: 0.53-0.76) for 5-year probability of pancreatic cancer. Five additional non-microbial metabolites were identified that when combined with the microbiome panel yielded an AUC of 0.79 (95% CI: 0.71-0.88) for 5-year probability of pancreatic cancer in the PLCO testing set. The combined metabolite panel and CA19-9 yielded an AUC of 0.86 (95% CI: 0.77-0.95) for 2-year probability of pancreatic cancer in the PLCO testing set, which was improved compared to CA19-9 alone (AUC: 0.70 (95% CI: 0.57-0.82), p< 0.001). Conclusion: We developed a metabolite panel derived in part from the microbiome for risk assessment of pancreatic cancer, which has relevance to prevention and early detection. Citation Format: Johannes F. Fahrmann, Ehsan Irajizad, Ana Kenney, Tiffany Tang, Jody Vykoukal, Ranran Wu, Jennifer B. Dennison, Marta Sans Escofet, James P. Long, Maureen Loftus, John A. Chabot, Michael D. Kluger, Fay Kastrinos, Lauren Brais, Ana Babic, Kunal Jajoo, Linda S. Lee, Thomas E. Clancy, Kimmie Ng, Andrea Bullock, Jeanine M. Genkinger, Anirban Maitra, Kim-Anh Do, Bin Yu, Brian M. Wolpin, Samir Hanash. Contribution of the microbiome to a metabolomic signature predictive of risk for pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P076.