Investigating the Development of Colorectal Cancer Based on Spatial Transcriptomics

Area of Science:

• Genomics
• Cancer Biology
• Spatial Biology

Background:

• Colorectal cancer (CRC) is a major global health concern.
• The spatial and temporal dynamics of CRC development are not well understood.

Purpose of the Study:

• To investigate intestinal tumor progression in APC Min/+ mice using spatial transcriptomics (ST).
• To identify key genes and pathways involved in CRC development and progression.

Main Methods:

• Spatial transcriptomics (ST) on APC Min/+ mouse intestinal tumors across multiple time points.
• Integrated dimensionality reduction and pathological annotation for cell type identification.
• Pseudo-time trajectory analysis and TCGA database analysis for gene expression dynamics.

Main Results:

• Distinct transcriptional profiles identified between tumor and normal tissues, resolving six cell types.
• Increased expression of MMP11 and MYL9 observed in later tumor progression stages.
• DEFA family genes, particularly DEFA3, were upregulated in normal tissues and inhibited cancer cell migration and proliferation in vitro.

Conclusions:

• Spatial transcriptomics is valuable for resolving spatiotemporal heterogeneity in colorectal cancer.
• MMP11/MYL9 and DEFA3 represent potential biomarkers and therapeutic targets for CRC.