Fig. 5: Squamous-like gene expression predicts aggressive disease and poor patient outcome.
From: Loss of colonic fidelity enables multilineage plasticity and metastasis
a, Representative IHC staining of a human CRC TMA for ATRX, HNF4A, CDX2 and LY6D. Examples of positive and negative staining are shown. Scale bar, 100 µm. b, Quantification of ATRX, HNF4A and CDX2 histoscore (H-score) values in LY6D– (<2% cells LY6D+) and LY6D+ (>2% cells LY6D+) tumour cores. n = 500 (ATRX, HNF4A) and 509 (CDX2) biologically independent samples. c, Representative IHC image of a LY6D-stained human stage IV primary tumour. Scale bars, 50 µm. d, Summary data indicating the percentage of human primary tumours at stages I–III versus stage IV positive for LY6D. The percentages are based on >2% cells LY6D+ and <2% cells LY6D–. P = 0.000027. e, Representative IHC image of LY6D-stained human liver metastasis. Scale bars, 100 µm. f, Summary data indicating the percentage of LY6D+ cells in matched human primary tumours and liver metastases. n = 17 biologically independent matched samples (7 data points are visible as 11 primary tumour samples have the same value (0) and are overlapping). g, UMAP plot of Juanito scRNA-seq dataset overlayed with iCMS designation. For comparison, AtrxKO, AtrxWT and AtrxKO/AtrxWT transcriptional expression scores are overlayed in the same data. h, Survival plot of Marisa CRC patient dataset separated on Atrx-based gene expression clusters. i, Volcano plot of HOMER TF enrichment analysis of TFs with differential motif accessibilities between HiSquam and HiCol signature tumours. Selected TF motifs in regions with reduced accessibility in HiSquam tumours highlighted in blue and TF motifs in regions with increased accessibility in HiSquam tumours highlighted in red. Data are the mean ± s.d. (b). P values were calculated using two-tailed Mann–Whitney tests (b), two-sided Fisher’s exact tests (d), two-tailed Wilcoxon matched-pairs signed-rank tests (f), log-rank (Mantel–Cox) tests (h) or two-sided Fisher’s exact test and adjusted for multiple comparisons with the Benjamini–Yekutieli method (i). NS, not significant.
