Abstract
Abstract Endometrial cancer (EC) rates are increasing in the United States, with 66,200 women diagnosed this year. The microbiome may be a key target for understanding EC etiology and progression and hold vital information for prevention strategies. With the largest cross-sectional cohort to date, a rich set of patient-related meta-data, and samples from multiple mucosal sites, we explored the gut-vagina axis in EC compared to benign gynecologic conditions. Vaginal and rectal swabs were collected from 192 patients diagnosed with benign conditions (n=108), hyperplasia (n= 18), and EC (n= 66). 16S rRNA amplicon sequencing was conducted on DNA samples, and data analysis was performed with QIIME 2 and R software. The clinical and demographic analysis identified risk factors associated with EC, such as BMI and menopausal status, that differed between disease groups. Global microbial analyses identified a distinct microbial composition between benign and EC, as well as higher diversity in rectal samples and lower diversity in vaginal samples in benign patients compared to cancer patients. Differential abundance analysis, even after adjustment for known risk factors, revealed unique microbial features such as depletion of Lactobacillus and increase of Anaerococcus, Porphyromonas, and Peptoniphilus in vaginal samples when EC is compared to benign conditions. While Rectal samples indicated a depletion of Peptoniphilus and Prevotella and an increase in Buttiaxella in EC compared to benign conditions. Additionally, community networks were different between cancer patients compared to benign, where taxa in Peptoniphilaceae had the most microbial network connections in EC compared to benign conditions. Notably, putative metabolic pathway analysis identified dysregulation of amino acid metabolism, complex carbohydrate metabolism, and hormone metabolism between cancer patients and benign, which provide key insight into the potential pathophysiological mechanisms employed by the microbiome in EC. This study provides key findings on unique singular and community microbial signatures that may directly affect EC development and be important targets for prevention. Citation Format: Nicole R. Jimenez, Chloe Herman, Pawel Laniewski, Emily K. Cope, Jamal Mourad, Nichole Mahnert, Dana M. Chase, J. G. Caporaso, Melissa M. Herbst-Kralovetz. Patients with endometrial cancer and benign gynecologic conditions exhibit unique vaginal and rectal microbiomes [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr PR005.