Investigating the Development of Colorectal Cancer Based on Spatial Transcriptomics

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. However, the spatial and temporal dynamics underlying its development remain poorly characterized. This study employs spatial transcriptomics (ST) to investigate the progression of intestinal tumors in APC ^Min/+ mice across multiple time points. We identified distinct transcriptional profiles between tumor and normal tissues, resolving six major cell types through integrated dimensionality reduction and pathological annotation. Pseudo-time trajectory analysis revealed increased expression of MMP11 and MYL9 in later stages of tumor progression. Analysis of human CRC cohorts from the TCGA database further confirmed that high expression of these genes is associated with advanced clinical stages and promotes tumor proliferation and invasion. Temporal gene expression dynamics indicated enrichment of cancer-related pathways concurrent with suppression of lipid and amino acid metabolism. Notably, genes in the DEFA family were significantly upregulated in normal tissues compared to tumor tissues. Functional validation showed that DEFA3 inhibits colon cancer cell migration and proliferation in vitro. These demonstrate the value of ST in resolving spatiotemporal heterogeneity in CRC and identify both MMP11/MYL9 and DEFA3 as potential biomarkers and therapeutic targets.