Single-cell transcriptome analysis elucidates the microenvironmental interactions between colorectal cancer and sarcopenia.

Colorectal cancer (CRC) often occurs in combination with sarcopenia (SP), which affects the prognosis of CRC, but the histopathological mechanisms underlying this process are unclear. Single-cell transcriptome technology provides a tool for resolving multi-organ pathological interactions, and previous studies have lacked direct molecular evidence of a trans-tissue microenvironment. To address this, we applied an integrated analytical approach. The integration of single-cell transcriptome data from 16 CRC tumor tissues (scRNA-seq) and 17 SP muscle tissues (snRNA-seq) was used to systematically resolve heterogeneity across tissue microenvironments using Harmony to correct for batch effects and combining cellular annotations, differential expression analyses, and CellChat communication modeling. Our analysis revealed that CRC and SP share 3 core cell types, namely, endothelial cells, fibroblasts and monocytes, but they show distinct transcriptional and functional differentiation in different tissues. CRC cells are enriched in the inflammatory, angiogenic and matrix remodeling pathways, accompanied by the upregulation of hypoxia-associated genes, whereas SP is biased toward muscle structural maintenance, metabolic regulation and repair functions. The MIF-CD74, COLLAGEN and THBS-CD47 pathways were active in CRC, whereas SDC4 and CD36-related signals were dominant in SP. VWF, PDGFRA and FCN1 were stably expressed in both groups, suggesting the existence of a conserved homeostatic regulatory network. In conclusion, this study reveals the cross-tissue functional heterogeneity of cell types shared by CRC and SP, suggests a set of potential pervasive regulators, and provides new perspectives for understanding the systemic effects of tumors and the microenvironmental mechanisms of sarcopenia.