Abstract 4890: Patients with high body mass index share tumor microbial profiles with CpG island methylator phenotype-high or early-onset colorectal cancers

Abstract Background: Tumor microbiota plays a significant role in colorectal cancer (CRC) by influencing tumor development and progression. Our previous study demonstrated a significant association between high body mass index (high BMI, BMI ≥ 27.5 kg/m2) and CpG island methylator phenotype-high (CIMP-high) in early-onset CRC (EOCRC, age < 50y). The present study investigates whether tumor microbiota may mediate this association in CRC. Materials and methods: We enrolled 140 patients with CRC and 30 patients with polyps from the biobank of National Taiwan University Hospital, respectively. The tumor and adjacent normal part in each tumor or polyp were collected. V3-V4 regions of bacterial 16S ribosomal RNA gene were amplified and then amplicons were sequenced on the MiSeq system. Patients’ clinicopathological characteristics were also recorded. CIMP status was defined by using a 5-gene panel (p16, MINT1, MINT2, MINT31 and MLH1) and MethyLight assay. Analysis of diversity and LefSe (Linear discriminant analysis Effect Size) of tumor microbiota were performed and the results were compared between each subgroup. Results: In total, 121 CRC tumors (CRC-T), 115 adjacent normal (CRC-N) and 26 polyps (polyp-T and polyp-N) passed the quality control (sequencing depth > 5000 reads). Microbiota α diversity is significantly lower in CRC compared to that in polyps (p = 1.3 x 10-11). Microbiota α diversity is also reduced in CRC patients with high BMI compared to those with low BMI (p = 0.042). LefSe analyses revealed specific microbiota enriched in each subgroup, including EOCRC, high BMI, and CIMP-high. The Venn diagram revealed multiple overlapping bacteria taxa between the high BMI and the CIMP-high or EOCRC subgroups. Conclusion: We found the diversity of microbiota in CRC with high BMI is significantly lower than that in CRC with low BMI and identified specific bacteria taxa shared between high BMI and CIMP-high or EOCRC tumors. The clinical applications of these bacterial taxa warrant further exploration. Citation Format: KuoHsing Chen, Jyh-Shiuan Hsu, Yu-Li Su, Shih-Chiang Lin, Been-Ren Lin, Kai-Lung Tsai, Li-Ming Tseng, Yi-Hsin Liang, Jia-Huei Tsai, Chien-Chen Tsai, Ting-Ting Liu, Mong-Hsun Tsai, Kun-Huei Yeh. Patients with high body mass index share tumor microbial profiles with CpG island methylator phenotype-high or early-onset colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4890.