Sex-specific Phenotypes modulated by activin in pancreatic cancer cachexia and mortality

Cachexia frequently develops in patients with pancreatic ductal adenocarcinoma (PDAC) and contributes to cancer deaths.Sex differences have been observed in cancer cachexia; however, the underlying molecular mechanisms are far less addressed. We assessed sex difference in PDAC cachexia phenotypes in the KPC (Kras-G12D;Trp-R172H;Pdx1::Cre) genetically engineered mouse model of PDAC and profiled gene expression in the quadriceps skeletal muscles. Males with PDAC experienced earlier cachexia-onset than the female counterpart and activin blockade by ACVR2B/Fc reduced cachexia sympotomes in males but not females. PDAC induced earlier global transcritome alterations in males than females. Males and females were evaluated for PDAC tumor and cachexia initiation and progress and ACVR2B/Fc effects. Tumor and organ tissues were collected at early and late time points and the quadriceps muscles were subjected to molecular and transcriptome analysis.