Fig. 1

Ductal-neuroendocrine plasticity is associated with decreased survival. a Ductal-neuroendocrine lineage plasticity is observed in human PDA. Human PDA samples were stained with SYP and Pan-CK by IF. Co-staining cells are marked with white arrows. H&E from the same tumor sample are shown below. Scale bars indicate 100 μM. b Human PDA sample was stained with SYP by IHC. Examples of ductal-associated SYP positive cells are marked with white arrows. Scale bars indicate 100 μM. c, d Ductal-neuroendocrine lineage plasticity is associated with poor PDA patient survival. Human PDA samples were stained for SYP and Pan-CK and the total percentage of tumor epithelium co-staining for CK-SYP across entire sections was graded as ≤5% or > 5%, and correlated with disease-free survival c and time-to-recurrence d as described in the Methods section. For c, P = 0.007, log-rank test. For d, P = 0.017, one-tailed Mann Whitney test. e, f Ductal-neuroendocrine lineage plasticity can be detected in circulating tumor cells (CTCs) from patients with PDA. CTCs from patients with PDA were stained for PanCK and SYP e and the number of SYP positive or CK-SYP dual positive cells was quantified for each patient f. Scale bar indicates 25 µM. g Analysis of NEPC gene signature in mouse CTCs (red bars) and matched single parental tumor cells (black bars) from KPC mice (GSE51372). Samples were ranked based on ratios of NEPC UP vs. PCA UP (NEPC down) gene expression as described in the Methods section