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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 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.

The transcriptional repressor Rex has been implicated in the regulation of energy metabolism and fermentative growth in response to redox potential. Streptococcus mutans, the primary causative agent of human dental caries, possesses a gene that encodes a protein with high similarity to members of the Rex family of proteins. In this study, we showed that Rex-deficiency compromised the ability of S. mutans to cope with oxidative stress and to form biofilms. The Rex-deficient mutant also accumulated less biofilm after 3days than the wild-type strain, especially when grown in sucrose-containing medium, but produced more extracellular glucans than the parental strain. Rex-deficiency caused substantial alterations in gene transcription, including those involved in heterofermentative metabolism, NAD 1 regeneration and oxidative stress. Among the upregulated genes was gtfC, which encodes glucosyltransferase C, an enzyme primarily responsible for synthesis of water-insoluble glucans. These results reveal that Rex plays an important role in oxidative stress responses and biofilm formation by S. mutans.

The transcriptional repressor Rex has been implicated in the regulation of energy metabolism and fermentative growth in response to redox potential. Streptococcus mutans, the primary causative agent of human dental caries, possesses a gene that encodes a protein with high similarity to members of the Rex family of proteins. In this study, we showed that Rex-deficiency compromised the ability of S. mutans to cope with oxidative stress and to form biofilms. The Rex-deficient mutant also accumulated less biofilm after 3 days than the wild-type strain, especially when grown in sucrose-containing medium, but produced more extracellular glucans than the parental strain. Rex-deficiency caused substantial alterations in gene transcription, including those involved in heterofermentative metabolism, NAD(+) regeneration and oxidative stress. Among the upregulated genes was gtfC, which encodes glucosyltransferase C, an enzyme primarily responsible for synthesis of water-insoluble glucans. These results reveal that Rex plays an important role in oxidative stress responses and biofilm formation by S. mutans.