Profiling the heterogeneity of colorectal cancer consensus molecular subtypes using spatial transcriptomics.

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Consensus Molecular Subtypes (CMS) classify colorectal cancer (CRC) but are limited by intratumoral heterogeneity.
• Understanding CRC's cellular and molecular composition is crucial for clinical application and personalized therapy.

Purpose of the Study:

• To decipher the spatially resolved cellular and molecular composition of colorectal cancer (CRC).
• To map intratumoral heterogeneity of CMS and their microenvironment.
• To identify cell communication events at the tumor-stroma interface.

Main Methods:

• Utilized Spatial Transcriptomics (ST) combined with single-cell RNA sequencing (scRNA-seq).
• Analyzed the spatial distribution of cells and molecular features within CRC tumors.
• Investigated cell-cell interactions in the tumor microenvironment.

Main Results:

• Mapped intratumoral heterogeneity of CMS and their associated microenvironments.
• Identified specific cell communication events in CMS2 carcinomas, including tumor growth-modulating signals.
• Discovered potential regulation of ETV4 by DCN and PLAU-PLAUR ligand-receptor interactions at the tumor-stroma interface.

Conclusions:

• Spatial transcriptomics (ST) is a powerful tool for resolving CRC molecular heterogeneity.
• Characterizing the spatial architecture of CRC can advance the development of personalized therapies.
• Understanding tumor-stroma interactions provides novel targets for CRC treatment.