Abstract 3682: Body mass index impacts blood-based markers signatures in advanced colorectal cancer

Abstract Background: In the USA it is estimated that more than half-million cancer cases are associated with obesity. Colorectal Cancer (CRC) is one of the most common types of cancer, and rising death rates underscores the need for a feasible and tailored algorithm to aid in disease management such as a blood-based test, i.e., liquid biopsy. Here, we investigate a multimodal assessment of blood-based markers, cell-free DNA (cfDNA) methylation signatures, levels of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Carcinoembryonic Antigen (CEA), and the impact of Body Mass Index (BMI) in CRC cases at presentation. Method: A multimodal assessment was conducted on sixteen treatment-naive CRC cases. The evaluation consisted of a review of clinical records to collect (i) blood levels of CEA, AST, and ALT, and (ii) BMI data. Additionally, cfDNA methylation analysis was performed by Whole Genome Bisulfite Sequencing (WGBS), and methylated SEPTIN9 (mSEPT9) by Real-Time PCR. Statistical analysis was conducted on GraphPad and SPSS. Results: All CRC cases were advanced stages (III and IV), and most had a familial history of cancer. The mean age of diagnosis was 51.50 years (SE ± 3.42). Healthy BMI was observed in most cases (56.3%), followed by overweight/obese (31.3%) and underweight (12.5%). ALT, AST, and CEA levels were abnormal in 25%, 31.3%, and 56.3% of the cases, respectively. Overall cfDNA analysis showed aberrant methylation patterns in all cases, and 75% were mSEPT9 positive. Principal component analysis (PCA) showed a significant correlation among AST (0.93), CEA (0.89), ALT (0.83), mSEPT9 positivity (0.80), and cfDNA overall methylation (0.50) (Kaiser-Meyer-Olkin score 0.60, Bartlett's test p<0.05) but negative correlation with BMI (-0.33) (Kaiser-Meyer-Olkin score 0.50, Bartlett's test p<0.05). Conclusion: Blood-based multimodal assessment could be a valuable method for managing CRC clinically. However, there is an inverse correlation BMI and blood markers. This highlights the importance of considering BMI when evaluating liver function and tumor markers in advanced CRC cases. Citation Format: Gabriela Felix, Jun Gong, Francesca Aguirre, Lisa Zhou, Aaron Denmark, Rocio Ramirez, Hayan Lee, Megan Hitchins. Body mass index impacts blood-based markers signatures in advanced colorectal cancer [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 3682.