The Time-Course of Cancer Cachexia Onset Reveals Biphasic Transcriptional Disruptions in Female Skeletal Muscle Distinct from Males

Cancer-cachexia (CC) is experienced by 80% of cancer patients, representing up to 40% of cancer-related deaths. Evidence suggests biological sex dimorphism associated with cancer-cachexia. Assessments of the female transcriptome in cancer-cachexia are lacking and direct comparisons between biological sex are scarce. The purpose of this study was to define the time course of LLC-induced CC in females using transcriptomics, while directly comparing biological sex dimorphisms. Gastrocnemius of male and female mice (n=8/group) were collected at 1-, 2-, 3-, 4-weeks of tumor progression. Due to dichotomous effect in tumor growth in female mice, animals were reorganized into low tumor (LT; tumor mass≤1.2g) and high tumor (HT; tumor mass≥2g). Male RNA sequencing data has been previously published (Gene Expression Omnibus accession number GSE114820). RNA sequencing of total muscle was re-analyzed similarly to females.