Myosteatosis is associated with reduced survival in patients with pancreatic adenocarcinoma undergoing curative intent resection

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We included 203 patients undergoing curative-intent surgery for PDAC between 2011 and 2022. Autosegmentation of cross-sectional CT slices quantified skeletal muscle area and fat infiltration to identify patients with sarcopenia and myosteatosis. Cox proportional hazards modeling was used to evaluate survival. Pre-operative serum and intra-operative rectus abdominis biopsies underwent metabolomic and transcriptomic profiling, respectively. Of 203 patients, 116 had sarcopenia and 120 had myosteatosis. Median follow-up was 33.5 months. On multivariable analysis, myosteatosis but not sarcopenia predicted shorter OS, with the association limited to male patients with myosteatosis (median OS 16.3 vs 39.9 months, log-rank P<0.001). In 57 muscle transcriptomes, sex explained the largest variance, with <1% overlap in myosteatosis-related differentially expressed genes between sexes and <15% for sarcopenia. EnrichR and Ingenuity Pathway Analysis revealed upregulation of pro-inflammatory pathways in males and downregulation in females with myosteatosis. Serum metabolomics revealed altered glutathione metabolism in both sexes. Transcriptomic data can be found at: https://www.ncbi.nlm.nih.gov/sra/PRJNA1315257

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