Revisiting colorectal cancer tumorigenesis with spatially-resolved gene expression profiling

Early detection and treatment are paramount to the clinical outcome of patients with colorectal cancer (CRC). Deciphering the dynamic interactions that occur between epithelial cells and stromal cells during tumorigenesis requires in-depth analyses of early-stage CRC lesions in spatial context. Here we employed spatially-resolved gene expression profiling to dissect molecular processes that associate with malignant transformation in CRC. We provide the transcriptional landscapes of colorectal cancer tumorigenesis from healthy mucosa, through different degrees of dysplasia, to cancer. The complementary examination of epithelial and stromal fractions allowed us to define whether specific oncogenic processes involved cancer cells, stromal cells, or the tumor microenvironment as a whole. We identified several genes that were consistently deregulated during CRC onset that could serve as clinical biomarkers for early-stage CRC. Furthermore, we uncovered an essential role for the innate immune system during CRC tumorigenesis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/462502v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@c24d1forg.highwire.dtl.DTLVardef@554113org.highwire.dtl.DTLVardef@1236f99org.highwire.dtl.DTLVardef@173ac8c_HPS_FORMAT_FIGEXP M_FIG C_FIG