Tumor-Derived Sarcopenia Factors Are Diverse in Different Tumor Types: A Pan-Cancer Analysis.

Cancer-associated muscle wasting is a widespread syndrome in people with cancer and is characterized by weight loss and muscle atrophy, leading to increased morbidity and mortality. However, the tumor-derived factors that affect the development of muscle wasting and the mechanism by which they act remain unknown. To address this knowledge gap, we aimed to delineate differences in tumor molecular characteristics (especially secretion characteristics) between patients with and without sarcopenia across 10 tumor types from The Cancer Genome Atlas (TCGA). We integrated radiological characteristics from CT scans of TCGA cancer patients, which allowed us to calculate skeletal muscle area (SMA) to confirm sarcopenia. We combined TCGA and GTEx (The Genotype-Tissue Expression) data to analyze upregulated secretory genes in 10 tumor types compared with normal tissues. Upregulated secretory genes in the tumor microenvironment and their relation to SMA were analyzed to identify potential muscle wasting biomarkers (560 samples). Meanwhile, their predictive values for patient survival was validated in 3530 samples in 10 tumor types. A total of 560 participants with transcriptomic data and SMA were included. Among those, 136 participants (24.28%) were defined as having sarcopenia based on SMA. Enrichment analysis for upregulated secretory genes in cancers revealed that pathways associated with muscle wasting were strongly enriched in tumor types with a higher prevalence of sarcopenia. A series of SMA-associated secretory protein-coding genes were identified in cancers, which showed distinct gene expression profiles according to tumor type, and could be used to predict prognosis in cancers (