Abstract 2909: Tumor microbiota profiles are associated with molecular subtype and survival in colorectal cancer patients

Abstract Background: The intestinal microbiome is intimately involved in the pathogenesis of colorectal cancer and likely holds further insights to improve the treatment and management of this deadly disease. In a clinical cohort of patients with colon and rectal cancers, we characterized the tumor microbiota of surgical specimens and evaluated associations with prognostic factors, consensus molecular subtypes (CMS), and survival. Methods: In 167 patients diagnosed with stage II through IV colon and/or rectal cancer who underwent evaluation and surgical resection (no prior systemic therapy) at The University of Texas MD Anderson Cancer, we characterized the tumor microbiome via 16S rRNA gene sequencing. Each patient's tumor was classified via CMS, a gene expression-based colorectal cancer classification system; and all patients were prospectively followed for disease progression, recurrence, or death. Microbiota diversity and composition were assessed with regard to clinicopathologic and tumor features; and associations with survival were further evaluated in multivariable Cox proportional hazards models. Results: Left- vs. right-sided colon tumors were characterized by higher microbial diversity, distinct community features, and increased abundance of Bacteroides and Fusobacterium. CMS1 (microsatellite instability immune) vs. CMS2 (canonical) tumors were characterized by higher Bacteroides and Fusobacterium and lower Escherichia (all P<0.05). Fusobacterium-positive and Escherichia-positive tumors were associated with improved 5-year overall survival [presence vs. absence, multivariable-adjusted HR and 95% CI: 0.43 (0.20-0.93) and 0.32 (0.19-0.78), respectively]. Bacteroides was enriched among stage II/III patients who progressed within 2-years (log-rank p<0.001). Conclusions: Our findings are consistent with those of other groups suggesting the landscape of the tumor microbiome differs by sidedness and molecular subtype, holding important clues and exploitable targets to improve outcomes in colorectal cancer patients. Citation Format: Fangyu Li, Michael G. White, Jennifer Davis, Kristi L. Hoffman, David Menter, Nadim Ajami, Xiaotao Zhang, Jeffrey S. Morris, Robert R. Jenq, Joseph Petrosino, Jennifer A. Wargo, Scott Kopetz, Carrie R. Daniel. Tumor microbiota profiles are associated with molecular subtype and survival in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2909.