Murine pancreatic tumors induce pathological remodeling of muscles critical to chewing and swallowing [RNA-seq]

Myofiber cross-sectional area was reduced by 42% in the masseter and 23% in the digastric. RNA sequencing revealed distinct transcriptional responses between these muscles. The masseter muscle showed enrichment of catabolic signaling pathways, including proteolytic and stress-response programs, alongside downregulation of extracellular matrix and growth-related programs.

In contrast, the digastric muscle exhibited robust upregulation of immune and inflammatory pathways, including innate and adaptive immune signaling, with minimal overlap between muscles. Collectively, these findings demonstrate that pancreatic cancer drives pathological remodeling and atrophy in muscles central to chewing and swallowing while eliciting distinct, muscle-specific transcriptional responses, changes that could negatively affect food and nutrient intake and thereby contribute to cachexia progression.