Abstract 6688: Differential serum mirnas in obese and diabetic African American colon adenoma patients

Abstract Background: Metabolic syndrome, characterized by obesity, diabetes, and other metabolic disturbances, is associated with an increased risk of colon cancer. There is a critical need for assays that can detect biomarkers to enable risk stratification, early diagnosis, and prevention of colon adenomas and colorectal cancer. Serum miRNAs are emerging as promising biomarkers for this purpose. Aim: The purpose was to elucidate the role of miRNAs in the pathophysiology of colon adenomas in the context of obesity and diabetes. Methods: We used serum samples from age- and gender-matched African Americans (n=18 per group) to ensure that the comparison of miRNA expression was not confounded by age or gender differences. The groups included patients without adenomas (Normal), patients with adenomas and obesity, and patients with adenomas and diabetes. RNA extraction and miRNA sequencing was rigorous, utilizing the miRNeasy Serum/Plasma Kit and Lexogen Small RNA-Seq Library Prep Kit, respectively. Illumina NextSeq 500 sequencing provided high coverage (15 million reads per sample). The alignment to the UCSC hg38 human genome and the use of the DESeq2 R package for differential expression analysis ensured robust statistical evaluation of miRNA expression changes. We identified miRNAs with significant fold changes (log2 FC ≥ 2 or ≤ -2) and p-values < 0.05.Results: In the Adenoma-Obese group, miR-455, miR-219b, miR-34a, miR-378a, miR-485, and miR-133b showed significant associations with obesity-related metabolic dysregulation. Notably, miR-34a, involved in cell cycle and apoptosis regulation, was upregulated, highlighting its role in obesity-related cancer pathogenesis. In the Adenoma-Diabetic group, miR-455 was upregulated, suggesting its involvement in insulin resistance and adenoma progression, while miR-219b was downregulated, potentially reflecting a compensatory response to hyperglycemia. Ingenuity Pathway Analysis (IPA) revealed that these miRNAs are linked to pathways involved in cancer, diabetes, and lipid metabolism. Key pathways, including insulin signaling, Wnt/β-catenin, and mTOR, underscore the interplay between metabolic disorders and colorectal adenoma progression. Conclusion: This study highlights distinct miRNA expression profiles associated with adenoma development in obesity and diabetes. miR-34a, miR-378a, and miR-455 emerged as potential biomarkers and therapeutic targets. Future research should validate these findings in larger cohorts to refine their utility in clinical applications. Citation Format: Hassan Brim, Adeyinka O. Laiyemo, Hassan Ashktorab. Differential serum mirnas in obese and diabetic African American colon adenoma patients [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 6688.