Fig. 4: Multiomics and eco-spatial analysis improves prognostic capabilities for CRC.

a, Visualization of tissue samples from CLR and DII patients: (1) the cell-type map (top), (2) the diversity heatmap (middle, red: higher diversity, blue: lower diversity) and (3) the map of the diversity hot spots and cold spots (bottom). b, Quantitative assessment of MESA diversity metrics in CLR (n = 17) and DII (n = 18) tissues (same sample size for b and d). Standard box plot metrics were used throughout. The analysis highlighted significant differences in spatial diversity patterns, with CLR tissues showing higher MDI (P = 0.018), GDI (P = 0.006) and DPI (P = 0.046), indicative of distinct spatial patterns between the two CRC subtypes. Statistical comparisons are conducted using two-sided Welch’s t-test. c, Kaplan–Meier survival curves stratify CRC patients using pathologist-annotated CLR/DII classification and MESA diversity metrics. Two-sided log-rank tests show significant stratification for both approaches, with MESA metrics demonstrating a lower P value. Cox proportional hazards models demonstrate improved performance using MESA metrics based on the concordance index (C-index: 0.734 ± 0.106) over CLR/DII annotation (0.717 ± 0.088), with further improvement when combined (0.763 ± 0.085). d, Abundance of B cells, T_reg cells and T_reg cell cohabitation frequencies with CD68⁺CD163⁺ macrophages in CLR and DII tissues. Notably, the distinctions between CLR and DII are more pronounced within hot spots versus whole tissue, achieving lower P values based on two-sided Welch’s t-test with BH FDR correction. e, Circos plots illustrate cellular abundance and cohabitation frequencies, where nodes represent distinct cell types and edges represent cohabitation relationships. Node size corresponds to cell-type abundance, whereas edge thickness denotes cohabitation strength. f, DE and gene set enrichment analyses reveal unique gene expression patterns distinguishing CD68⁺CD163⁺ macrophages located in hot spots versus cold spots. DE was performed with a two-sided exact test and GSEA with a two-sided permutation-based tests; all P values have been adjusted using the BH procedure. The adjusted P value threshold in DE was set at 0.05 and the effect size (log fold-change) threshold at 0.1.