Abstract 5914: Colorectal cancer attributes and outcomes according to Fusobacterium nucleatum enrichment and presence
Authors: Hill Courtney M. , Hullar Meredith A. , Reedy Adriana , Malen Rachel , Ammar Hamza , Kahsai Orsalem , Ma Ningxin , Ogino Shuji , Randolph Timothy , Newcomb Polly , Phipps Amanda 
Published: April 2023

Purpose: Fusobacterium nucleatum (Fn) has been associated with colorectal cancer (CRC) etiology and outcomes. However, these relationships may differ by tumor attributes. We examined whether Fn enrichment and presence in CRC was associated with tumor attributes and survival.

Experimental Design: We measured the abundance of Fn via droplet digital PCR in patient-matched CRC tumor and normal tissue samples from a subset of participants in the Puget Sound CRC Cohort (n=526). Fn enrichment was defined as the continuous difference in Fn abundance (normalized to counts of a host housekeeping gene) between patient-matched tumor and normal tissue samples. Fn presence in tumor was classified categorically as negative, low (Fn abundance &gt;0 but &lt;median level among those positive for Fn), or high (abundance ≥median). Fn enrichment and presence variables were examined in relation to tumor attributes (site, stage, microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutation status), molecular subtypes, and CRC survival. Molecular subtypes were defined as: type 1 (MSI-high, CIMP-high, BRAF-mutated); type 2 (microsatellite stable [MSS]/MSI-low, CIMP-high, BRAF-mutated); type 3 (MSS/MSI-low, non-CIMP, KRAS-mutated); type 4 (MSS/MSI-low, non-CIMP, BRAF- and KRAS-wildtype); and type 5 (MSI-high, non-CIMP, BRAF- and KRAS-wildtype). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations of Fn enrichment and presence with tumor attributes, adjusted for age, sex, tumor site, and Fn abundance in normal tissue (Fn enrichment only). Cox regression was used to estimate hazard ratios (HR) and 95% CIs for the associations of Fn enrichment and presence with CRC survival, adjusted for age, sex, tumor site, tumor markers, and Fn abundance in normal tissue (Fn enrichment only).

Results: High Fn presence was negatively associated with left-sided colon and rectal tumors. While Fn enrichment was only significantly associated with CIMP-high status (OR 1.2; 95% CI 1.0, 1.4; p=.03), high Fn presence was positively associated with MSI (OR 4.9; 95% CI 2.8, 8.4; p&lt;.001), CIMP-high (OR 3.2; 95% CI 1.8, 5.7; p&lt;.001), and BRAF-mutated status (OR 3.3; 95% CI 1.8, 6.1; p&lt;.001). Fn enrichment was associated with higher odds of type 2 tumor classification (OR 1.2 95% CI 1.0, 1.5; p=.03) and high Fn presence was associated with higher odds of type 1 (OR 5.8; 95% CI 2.3, 15.0; p&lt;.001) and type 5 tumor classification (OR 3.4; 95% CI 1.1, 10.4; p=.03). Continuous Fn enrichment was independently associated with lower survival (HR 1.1; 95% CI 1.0, 1.1; p=.006) but high Fn presence was not (HR 1.0; 95% CI 0.6, 1.6; p=.99).

Conclusions: Our findings suggest that Fn enrichment and presence are associated with certain CRC tumor attributes and survival, but associations varied by how Fn status was defined.

Citation Format: Courtney M. Hill, Meredith A. Hullar, Adriana Reedy, Rachel Malen, Hamza Ammar, Orsalem Kahsai, Ningxin Ma, Shuji Ogino, Timothy Randolph, Polly Newcomb, Amanda Phipps. Colorectal cancer attributes and outcomes according to Fusobacterium nucleatum enrichment and presence [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 5914.