Fig. 5: NGFR⁺ /PDGFRα⁺ cells are linked to lobular invasion and an inflammatory microenvironment.

a Representative multiplex-immunofluorescence (m-IF) of stromal markers. Magnifications show tumor^in_lobule intermixed with parenchymal structures embedded in NGFR⁺ stroma. Right panel: corresponding HE region. b Expression of NGFR, alpha-smooth muscle actin (ASMA), cluster of differentiation (CD)74, vimentin, and platelet-derived growth factor receptor alpha (PDGFRα). Inner layer: within 15 µm from tumor, middle: 15–30 µm, outer: 30–45 µm. Unpaired two-tailed Kruskal–Wallis rank sum test, with post-hoc Dunn’s test. c Stromal cell expression within 45 µm to tumor. Unpaired two-tailed Wilcoxon rank sum test. d, e Proportional Venn diagrams of overlapping marker expression within the NGFR⁺ population from m-IF (d), and with the NGFR⁺ populations from murine pancreatic ductal adenocarcinoma (PDAC)⁴¹ (e, left; n = 977 cells, n = 12 mice) and two human PDAC datasets^42,43 (Peng et. al., middle; n = 659 cells and n = 24 patients, and Kim et al., right; n = 1056 cells and n = 17 patients). f Gene Ontology (GO, biological processes) enrichment analysis of significantly upregulated genes in NGFR⁺ fibroblasts compared to other fibroblasts present in murine PDAC (n = 12 mice). Bonferroni–Hochberg (BH)-corrected Fischer’s Exact test. g Schematic of longitudinal orthotopic injection PDAC model⁴¹, which included n = 3 normal pancreata. Cells for injection originated from Kras^G12D/+;Trp^R172H/+;Pdx1^cre/+(KPC) mice. scRNA-seq: single-cell RNA sequencing. h Signatures overlayed to the longitudinal orthotopic injection model of murine PDAC. Data from n = 9 mice. i NGFR and CAF signatures in human PDAC across tumor size; T1 < 2 cm, T2 2–4 cm, T3 > 4 cm. Data from n = 24 patients (Peng et al.) b, c BH-correction applied. BH-corrected p-values are given. Box-and-Whisker plots show the median (line), the interquartile range (IQR, box) and minimum and maximum values within 1.5 times IQR from the first and third quartile (whiskers). n = 363 ROIs (222 stromal, 141 lobular; 121 per layer). a–d Data from n = 8 individual tumors. Source data are provided in the Source Data file.