Fig. 2: Bulk RNA sequencing and genomic alteration assessment of baseline tumors.

A Volcano plot showing log2-transformed Fold Change (log2FC) in protein-coding genes in patients with progression of disease (PD) versus progression-free ones (PF). While no statistically significant gene was detected, orange and dark gray dots correspond to the most upregulated genes in PF and in PD samples, respectively. B Gene set variation analysis (GSVA) on MSigDB Hallmark gene sets. PF and PD samples are annotated in orange and gray, respectively. C Gene set enrichment analysis (GSEA) showing epithelial-mesenchymal transition (EMT), angiogenesis, KRAS signaling up, interferon-gamma response, and interferon-alpha response Hallmark gene sets from MSigDB that are significantly enriched in the tumors of PF (orange) versus PD (gray) patients (Benjamini–Hochberg adjusted p < 0.05). Fold change expression values and adjusted p values were combined to rank the genes as input for the GSEA which is based on the Kolmogorov–Smirnov test. D Volcano plot highlighting the protein-coding genes with the highest FC for the following signatures: Angiogenesis (in red) and EMT (in green) pathways—enriched in PD; Interferon-alpha (yellow) and interferon-gamma (dark blue) pathways—enriched in PF. None of the highlighted genes was statistically significant. In all panels, n = 11 for PF and n = 4 for PD (biologically independent samples). The complete list of the genes that are enriched in the pathways of the GSEA analysis are provided in Supplementary Data 1.