Abstract 2364: Gut microbiome interacts with clinical characteristics on all-cause mortality of colorectal cancer patients
Authors: Hoang Tung , Kim Min Jung , Park Ji Won , Jeong Seung-Yong , Shin Aesun 
Published: April 2023

Background: Gut microbiota has been introduced to involve in the migration and invasion stage of metastasis of colorectal cancer (CRC) cells and interact with both the pharmacokinetics and pharmacodynamics of chemotherapeutic agents and immune checkpoint inhibitors. In this study, we examined microbiome features in association with all-cause mortality of CRC patients and examined their interactions with clinical factors.

Methods: We performed 16S rRNA sequencing for 331 preoperative fecal samples of CRC patients at Seoul National University Hospital, Korea. Multiple Cox proportional hazard model was applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of all-cause mortality due to microbiome features (within-sample diversity indices, species patterns, genus abundance, and taxonomic co-occurrence networks) and clinical factors (tumor grade and stage, surgical methods, neoadjuvant and adjuvant therapies, and invasion). We added the multiplicative term into the model to test the interaction between gut microbiota and clinical characteristics.

Results: During a median follow-up of 3.7 years, deaths from any causes were reported in 46 patients. From 172 species, the principal component analysis identified 4 patterns, which explained a total 66.1% variation in species abundance. Of 77 genera, 9 co-occurrence networks were identified by the SParse InversE Covariance Estimation for Ecological Association Inference. For genus level, the risk of death was positively associated with Butyricicoccus (HR=1.54, 95% CI=1.17-2.04), but inversely associated with Lactococcus (HR=0.60, 95% CI=0.37-0.95), Acidaminococcus (HR=0.57, 95% CI=0.34-0.96), Megasphaera (HR=0.79, 95% CI=0.64-0.99), Mitsuokella (HR=0.75, 95% CI=0.57-0.99). All-cause mortality was associated with well or moderately differentiated adenocarcinoma (HR=3.84, 95% CI=1.83-8.07), neoadjuvant therapy (HR=4.10, 95% CI=1.40-12.0), tumor stage IV (HR=8.64, 95% CI=3.42-21.8), and presence of venous invasion (HR=2.32, 95% CI=1.08-4.97). Among clinical pathological factors associated with all-cause mortality, Bacteroides abundance significantly interacted with both tumor stage (pinteraction=0.013) and venous invasion (pinteraction=0.001).

Conclusion: Our study identified several microbiome features in links with either increasing or decreasing mortality from any causes. Interactions between the gut microbiome and clinical factors might inform insights on how the gut microbiota modulates the effect of clinical factors on CRC prognosis after the curative operation. Further research using postoperative information is needed to confirm our findings.

Citation Format: Tung Hoang, Min Jung Kim, Ji Won Park, Seung-Yong Jeong, Aesun Shin. Gut microbiome interacts with clinical characteristics on all-cause mortality of colorectal cancer patients [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 2364.