Fig. 2: Transcriptional landscape of siNETs defines four molecular features and the mesenchymal character predicts poor prognosis.

Exploring the transcriptional landscape of siNETs by RNA-sequencing. a Determination of the optimal number of gene clusters in the siNETs cohort with consensus clustering based on the 10% most variant genes among the discovery cohort of siNETs. CDF (Cumulative Distribution Function) b Leiden clustering analysis (w/ 4 clusters) projected in UMAP-2D plan. c Pathway enrichment analysis of the 4 siNETs cluster described in (a, b) (epithelial in green, vesicular in red, immune in blue and mesenchymal in gold). Adjusted two-tailed p-values (hypergeometric test) are shown on each bar (BH: Benjamini-Hochberg). d Hierarchical clustering (clustering method: Ward’s; distance: Euclidean): genes (row) are split according to the Leiden gene expression clusters: epithelial (green), vesicular (red), immune (blue), mesenchymal (gold). Recapitulative ssGSEA score of each cluster is indicated as bottom annotation (see Supplementary Fig. 2). TPM (Transcripts Per Million). e Kaplan-Meier, log-rank test and Cox proportional hazards regression model methods were used to study overall (OS) survival for epithelial, vesicular, immune, mesenchymal statuses respectively in green, red, blue and gold. The shaded areas represent 95% confidence intervals around the curves; the median survival rate is represented by dotted line; p-values are indicated below the graphs.