Circulating <scp>microRNA</scp> signatures of cachexia and cancer in <i>Canis familiaris</i> as a comparative oncology model for human disease

Cachexia, a severe muscle-wasting syndrome, lacks objective biomarkers for early detection. This study aimed to identify circulating microRNA signatures for cachexia and cancer in senior dogs, a comparative oncology model for human disease. Serum microRNA expression was quantified in a cohort of 25 dogs, clinically classified by cachexia and cancer status. We identified a distinct signature for cachexia, with significant downregulation of miR-15a, miR-15b, miR-16, and miR-140. Circulating miR-16 emerged as the most robust individual biomarker for cachexia (AUC = 0.899). Furthermore, a sex-specific analysis revealed that miR-140 was significantly lower in female dogs with cancer compared to noncancer controls (P = 0.045), consistent with a sex- and disease-specific dual suppression mechanism involving estrogen receptor signaling and cachexia-driven systemic inflammation (corrected AUC = 0.667). These findings suggest circulating microRNAs as promising, noninvasive biomarkers for canine cachexia and highlight miR-140 as a candidate sex-specific biomarker for female cancers, warranting validation in larger cohorts. This work reinforces the value of the domestic dog as a spontaneous model for translational biomarker discovery.