Spatial Domain-Based Approach to Analyze the Mechanism of Sparganii Rhizoma-Curcumae Rhizoma Pair in the Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is a global health challenge shaped by a complex tumor microenvironment (TME), where myeloid-driven inflammatory and immunosuppressive processes play central roles. Understanding the spatial and dynamic interactions within the TME is essential for uncovering novel regulatory mechanisms. We integrated spatial transcriptomics, single-cell RNA-sequencing, and network pharmacology to develop a comprehensive analytical framework for deconstructing cellular and molecular interactions across spatial domains within the TME. Using this approach, we investigated the potential mechanisms by which the Sparganii Rhizoma-Curcumae Rhizoma (SCP) Chinese medicine (TCM) herbal pair may influence primary CRC and liver metastases. Our analysis suggests that in primary CRC, SCP may affect neutrophil-enriched domains through modulation of CEACAM-related signaling, while in liver metastases, it may influence macrophage-dominated domains associated with APP signaling. These findings highlight possible domain-specific molecular interactions and suggest that SCP may regulate intra- and inter-domain signaling patterns relevant to TME remodeling. This study establishes a novel integrative methodology to investigate spatial domain-specific mechanisms within the TME. Our findings reveal the multi-dimensional effects of SCP, providing a precision-targeted, TME-centric therapeutic strategy for CRC. The framework aligns with TCM principles and offers new avenues for personalized cancer therapies.