Abstract 355: Examination of systemic myokine concentrations with risk of cachexia in non-metastatic colorectal cancer patients - Results from the ColoCare Study

Abstract BACKGROUND: Cachexia is a multifactorial metabolic syndrome associated with higher risk of mortality. The precise molecular mechanisms and biological pathways involved remain poorly characterized. A specific criterion of cachexia is loss of muscle mass. Myokines affect muscle mass and have profound effects on glucose and lipid metabolism, thus contributing to energy homeostasis and potentially cachexia. Only sparse data for patients with non-metastatic colorectal cancer exist. This study aims to investigate associations of systemic myokine concentrations with onset of cachexia in non-metastatic colorectal cancer patients. METHODS: Serum samples from n=125 colorectal cancer patients (stage I-III) recruited from the ColoCare Study site at Huntsman Cancer Institute were collected prior to surgery (baseline). Assays were run with the Milliplex Human Myokine Magnetic panel containing beads such as FABP3, Oncostatin M, and FGF21. Patients were defined as cachectic, pre-cachectic, or non-cachectic based on the criteria by Fearon et al. based on sex, BMI, and weight loss over a period of six months. ANOVA were applied to analyze associations of myokines with cachexia at 12 month after surgery, adjusted by age at diagnosis, sex, tumor stage, and tumor site. RESULTS: At the 12 months follow-up, 11% of patients were diagnosed with cachexia (n=14), 14% of patients with pre-cachexia (n=18), and 74% of patients were defined as non-cachectic. Patients with cachexia were more likely to be diagnosed with rectal cancer (57%) compared to pre-cachectic (17%) or non-cachectic patients (42%; p<0.01). Patients who received neo-adjuvant treatment were more likely to be cachectic compared to pre-cachectic or non-cachectic patients (36% vs 11% vs 26%, respectively, p<0.01). FABP3 at baseline was significantly different across the three groups, e.g., FABP3 was 11.4 pg/ml for cachectic patients, 10.5 pg/ml for pre-cachectic patients, and 10.4 pg/ml for non-cachectic patients (p=0.02). FABP3 was associated with 65% increased risk of cachexia in unadjusted models, e.g., Odds ratio 1.65, 95% Confidence Intervals 1.05-2.61; p=0.03). After additional adjustment for age, sex, tumor site, and tumor stage the result was non-significant (p=0.26). There were no statistically significant differences in FGF21 and Oncostatin M concentrations across cachexia stages. C ONCLUSIONS: Cachectic patients presented higher FABP3 concentrations (p=0.02) which were associated with increased risk of cachexia, however these results were not significant after adjustment. In this study, cachectic patients were more likely to be diagnosed with rectal cancer. In summary, larger studies are needed to further evaluate FABP3 and other myokines as potential prognostic biomarkers for cachexia and consider differences by tumor site. Citation Format: Jennifer Ose, Ellen Beswick, Simon Ta Van, Richard H. Viskochil, Christy A. Warby, Jeffrey T. Yap, Matthew F. Covington, Anne H. Nguyen, Jordan W. Stanford, Tengda Lin, Anita R. Peoples, Sheetal Hardikar, Christopher I. Li, William M. Grady, David Shibatta, Adetunji T. Toriola, Martin Schneider, Jane C. Figueiredo, Daniel Jeong, Erin M. Siegel, Cornelia M. Ulrich, Biljana Gigic. Examination of systemic myokine concentrations with risk of cachexia in non-metastatic colorectal cancer patients - Results from the ColoCare Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 355.