Fig. 1

PI3K/Akt pathway plays a vital role in the resistance of PDAC to GEM-based chemotherapy. A, Overall experimental scheme for this study. B, Complex heatmap showing differentially expressed genes (DEGs) and distribution of clinical parameters between AG-sensitive and AG-resistant PDAC. C, KEGG pathway enrichment analysis for the upregulated DEGs in the RNA-seq comparing the AG-resistant group and AG-sensitive group. D, KEGG pathway enrichment analysis of external RNA-seq data, SRP303224. E, Representative hematoxylin and eosin (H&E) staining images of AG-sensitive and AG-resistant PDAC and patient-derived organoids (PDOs). Scale bar, 100 μm. F, IC₅₀ values for 10 PDOs after GEM treatment. G-H, Representative images of PDOs from PDO-AGS and PDO-AGR groups. PDOs treated for 48 h with nab-paclitaxel (10nM) and gemcitabine (30nM). Live/Dead cell viability staining showing live cells stained with calcein-AM (green) and dead cells with Ethidium-1 (red). Scale bar, 50 μm. I, RNA-seq results for PDO-AGS and PDO-AGR groups from PDOs. J, Heatmap showing DEGs between PDO-AGS and PDO-AGR groups. K, KEGG pathway enrichment analysis for upregulated DEGs in the RNA-seq comparing the PDO-AGS group and PDO-AGR groups. L, Representative images of H&E and IHC staining for p-Akt (Thr308) in PDOs from PDO-AGS and PDO-AGR groups