Fig. 2

Molecular characterisation of supra-carcinoids. a Forest plot of hazard ratios for overall survival of the supra-carcinoids, compared to Carcinoid A and B, and LCNEC. The number of samples (N) in each group is given in brackets. The black box represent estimated hazard ratios and whiskers represent the associated 95% confidence intervals. Wald test p-values are shown on the right. b Enrichment of hallmarks of cancer for somatic mutations in supra-carcinoids. Dark colours highlight significantly enriched hallmarks at the 10% false discovery rate threshold; corresponding mutated genes are listed in the boxes, and enrichment q-values are reported below. c Hematoxylin and Eosin (H&E) stains of three supra-carcinoids. In all cases, an organoid architecture with tumour cells arranged in lobules or nests, forming perivascular palisades and rosettes is observed; original magnification x200. Arrows indicate mitoses. d Radar charts of expression and methylation levels. Each radius corresponds to a feature (gene or CpG site), with low values close to the centre and high values close to the edge. Coloured lines represent the mean of each group. Left panel: expression z-scores of genes differentially expressed between clusters Carcinoid A and LCNEC or between Carcinoid B and LCNEC. Right panel: methylation β-values of differentially methylated positions between Carcinoid A and LCNEC clusters or between Carcinoid B and LCNEC clusters. e Radar chart of the expression z-scores of immune checkpoint genes (ligands and receptors) of each group. f Left panel: average proportion of immune cells in the tumour sample for each group, as estimated from transcriptomic data using software quanTIseq. Right panel: boxplot and beeswarm plot (coloured points) of the estimated proportion of neutrophils, where centre line represents the median and box bounds represent the inter-quartile range (IQR). The whiskers span a 1.5-fold IQR or the highest and lowest observation values if they extend no further than the 1.5-fold IQR. Data necessary to reproduce the figure are provided in Supplementary Data 1, 4, 5, 12, 17, and in the European Genome-phenome Archive