O060 - CIRCULATING MICRORNAS ASSOCIATED WITH SKELETAL MUSCLE MASS IN COLORECTAL CANCER: AN INTEGRATIVE BIOINFORMATIC AND PRELIMINARY CLINICAL ANALYSIS

O060

CIRCULATING MICRORNAS ASSOCIATED WITH SKELETAL MUSCLE MASS IN COLORECTAL CANCER: AN INTEGRATIVE BIOINFORMATIC AND PRELIMINARY CLINICAL ANALYSIS

K. POZZER ZUCATTI^1,2,*, M. A. Horst^2,3, K. L. Ford², B. R. da Silva², V. S. Chites^2,4, M. P. Sawyer⁵, M. Siervo⁶, M. Engelen⁷, N. E. Deutz⁷, C. M. Prado²

¹Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil, ²Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Canada, ³Federal University of Goias, Goiania, ⁴Federal University of Rio Grande do Sul, Porto Alegre, Brazil, ⁵Department of Oncology, University of Alberta, Edmonton, Canada, ⁶School of Population Health, Curtin University, Perth, Australia, ⁷Center for Translational Research in Aging and Longevity, Texas A&M University, Texas , United States

Rationale: Low skeletal muscle mass (MM) in colorectal cancer (CRC) is associated with worse clinical outcomes, but its molecular regulators remain unclear. This study aimed to identify circulating microRNAs (miRNAs) linked to both CRC and MM in a clinical trial.

Methods: Preliminary data from an ancillary analysis of the Protein Recommendation to Increase Muscle (PRIMe) trial were used. Bioinformatic analyses (DIANA-miRPath, miRTargetLink) identified miRNAs involved in CRC and MM-related pathways (mTOR, FoxO). Serum miRNA expression, appendicular lean soft tissue index (ALSTI), and dietary intake were analyzed in patients with stage II–IV of CRC at baseline and after 12 weeks of dietary intervention. Associations were evaluated using simple linear regression models.

Results: Six miRNAs overlapped across CRC, mTOR, and FoxO pathways (miR-19a, miR-17, miR-497, miR-27a, miR93, miR-130a). Longitudinal increases in miR-497 were positively associated with changes in ALSTI (β = 0.377, p = 0.044). At week 12, higher levels of miR-19a and miR-17 were inversely associated with MM, reaching statistical significance for miR-19a (β = -0.471, p = 0.004) and showing a trend for miR-17 (β = -0.329, p = 0.050). miR-27a at baseline showed positive associations with baseline ALSTI (β = 0.346, p = 0.039) and trends at week 12 (β = 0.326, p = 0.052). No consistent associations were observed for miR-93 or miR-130a.

Conclusion: Circulating miRNAs associated with CRC-related muscle loss appear to be linked to dysregulation of anabolic (mTOR) and catabolic (FoxO) pathways. Changes in MiR-497 and miR-19a expression showed the associations with MM, supporting their potential to identify patients with impaired anabolic responsiveness who may require tailored nutritional strategies, particularly in the context of protein intake.

Disclosure of Interest: K. POZZER ZUCATTI: None declared, M. Horst: None declared, K. Ford Other: honoraria from Abbott Nutrition, B. da Silva: None declared, V. Chites: None declared, M. Sawyer Speakers Bureau of: Viatris, Other: Viatris - Advisory board, M. Siervo: None declared, M. Engelen: None declared, N. Deutz Other: honoraria from Abbott Nutrition, C. Prado Consultant for: Abbott Nutrition, Nutricia, Novo Nordisk, Other: Speaker engagement: Abbott Nutrition, Nutricia, Nestle Health Science, Novo Nordisk