Determinants of early-onset cachexia in transgenic mouse model of pancreatic cancer

Since the lack of understanding of signaling mechanisms in cancer cachexia progress, the exact time point of cachexia onset remains unpredictable. To determine the molecular phenotypes of single cells at the utmost approximated timepoint of cachexia onset, we hypothesized that the tumor microenvironment and circulating blood cells could serve as biomarkers of cachexia-onset to map out the determinants of muscle wasting in a mouse model of cancer cachexia. Depending on individual tumors, subcutaneous syngeneic implantation of xenografts derived from the transgenic KrasG12D/+;Trp53flox/flox;Pdx1-Cre mouse model of pancreatic cancer-induced early-onset cachexia (EOCX) and Pre-cachexia (PreCX) in individual recipient mice. To characterize the dominants of cachexia-onset, immediate fresh collection of samples and processing for single-cell RNA sequencing, allowed the analysis of gene expression in the subcutaneous xenografted tumors and the peripheral blood mononuclear cells (PBMC) at the single-cell level. Our dataset classified high-quality cells-- 29,885 PBMCs and 24,925 subcutaneous tumor cells into subtypes. By dissecting the differentially expressed markers genes of EOCX versus the PreCX, these markers may represent the determinants of cachexia in multiple cell types in circulating PBMCs and in tumors at the single-cell resolution.