Abstract 6519: Tumor sidedness of colorectal cancer shows differential abundance of tumor microbiota and plausible implications

Abstract Background: The tumor microbiota in colorectal cancer (CRC) plays a significant role in carcinogenesis, progression and metabolic interaction. Studies have shown the microbiota composition may be different between left-sided and right-sided CRC (LCRC and RCRC). Materials and methods: We conducted a multi-cohort study to investigate the role of tumor microbiota in CRC in Taiwan. Cohort 1 included 140 CRC pairs from the National Taiwan University Hospital biobank. Cohort 2 was a prospective study to recruit patients with newly diagnosed CRC and collect their surgical specimens and physical activity status. Cohort 3 included 30 colon polyps. The V3-V4 regions of the bacterial 16S ribosomal RNA gene were amplified, and the amplicons were sequenced using the MiSeq system. Left-sided (LCRC, descending colon to rectum) and right-sided (RCRC, cecum to splenic flexture of transverse colon) CRC were defined according to the location of primary tumor. An integrated analysis of clinicopathological characteristics and tumor microbiota was conducted. Co-occurrence networks was used to understand the relationships and interactions between different microbial species within a community. Results: Among 140 CRC in cohort 1, 93 (66.4%) of them were left-sided. There were significantly more CIMP-high tumors in LCRC than in RCRC (p = 0.0002). The diversity of microbiota was not different between LCRC and RCRC. LefSe (Linear discriminant analysis Effect Size) analyses revealed many bacteria had significantly higher abundance in LCRC and RCRC (LDA score ≥ 2, p < 0.05). The top 3 microbiota were Bacillaceae, Sphingomonadaceae, Propionibacteriacea in LCRC and Enterococcus, Enterococcaceae, Lachnospiraceae in RCRC. Clinically, high abundance of Flavobacterium was significantly correlated to absence of high body mass index (BMI ≥ 27.5 kg/m2) (p = 0.0019) and low abundance of Lachnoclostridium was significantly associated with late-stage (stage 3 and 4) (p = 0.0363) in right-sided CRC. Co-occurrence networks and pathway analysis showed Flavobacterium was negatively associated with multiple nutrients metabolism. Conclusion: The microbiota composition between LCRC and RCRC was different. The clinical implications of Flavobacterium and Lachnoclostridium warrants further validation. Citation Format: Kuo-Hsing Chen. Tumor sidedness of colorectal cancer shows differential abundance of tumor microbiota and plausible implications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6519.