Fig. 3

Gene expression studies on LCNEC and SCLC. a The expression profiles of LCNEC and SCLC tumors were analyzed following the annotation and approach described in Fig. 2a. Expression values of genes identified by ClaNC (Methods section) are represented as a heatmap in which red and blue indicate high and low expression, respectively.  Selected candidate genes are shown on the right. Dashed green lines indicate an expression profile shared by LCNEC tumors with STK11/KEAP1 alterations (type I LCNECs). b The significant enrichment of differentially expressed genes and signaling pathways are displayed for type I LCNECs and type II LCNECs. P < 0.0001 (Methods section); * some SCLC tumors that co-clustered with type II LCNECs were included in this analysis. Key candidate genes are highlighted in bold. c, d Expression values for c the key neuroendocrine differentiation markers SYP (synaptophysin) and CHGA (chromogranin A) (scatter plot), and d NOTCH pathways genes (box plots: median and interquartile range, whiskers: min–max values). e Significant enrichment of differentially expressed genes and signaling pathways was analyzed for class I and II vs class III and IV tumor samples; P < 0.0001 (Methods section). f Expression values of SOX1, ELAVL3, and ELAVL4 are plotted for the clustering classes and other lung cancer subtypes (box plots: median and interquartile range, whiskers: min–max values). Q < 0.05 (#), SAM (Supplementary Dataset 12); P < 0.01 (**) Mann–Whitney U-test