Journal: bioRxiv
Article Title: Cross-species graph-embedding unmasks the ageing microenvironment as a key determinant of pancreatic cancer malignant cell biology and therapy response
doi: 10.64898/2026.02.02.703350
Figure Lengend Snippet: (A) Left: Graphical representation of the prioritization strategy for candidate drug targets within the inflammatory communities on GN moPDAC-old and GN huPDAC-old . Right: Graphical representation of the prioritization strategy for candidate drug targets within inflammatory-related communities on GN moMalign-old and GN huMalign-old . IRAK4 was the only common gene to both prioritization strategies. DGIdb, drug-gene interaction database. CPAT, canSAR.ai protein annotation tool. (B) Representative phospho-IRAK4 (p-IRAK4) stains in moPDAC-young and moPDAC-old. Scale bars, 50 μm. (C) Quantification of p-IRAK4 stain in moPDAC-young and moPDAC-old. Results show mean ± SEM. ***, P < 0.001, Mann-Whitney test. (D) Representative p-IRAK4 stains in huPDAC-young and huPDAC-old. Scale bars, 100 μm. (E) Quantification of p-IRAK4 stain in huPDAC-young and huPDAC-old. Results show mean ± SEM. *, P < 0.05, Mann-Whitney test. (F) Schematic of 2-week study in moPDAC-young and moPDAC-old tumour-bearing orthotopically grafted KPC PDAC organoid-derived mouse models with 100 mg/Kg IRAK4 inhibitor (IRAK4i, emavusertib, CA-4948) or vehicle by daily oral gavage. (G) Representative p-IRAK4 stains in vehicle- and IRAK4i- treated moPDAC-old. Scale bars, 50 μm. (H) Quantification of p-IRAK4 stain in vehicle- and IRAK4i- treated moPDAC-old. Results show mean ± SEM. **, P < 0.01, Mann-Whitney test. (I) Significantly upregulated and downregulated pathways identified by GSEA of IRAK4i-treated moPDAC-old (n=8) compared to vehicle-treated moPDAC-old (n=9). (J) Representative cleaved caspase 3 (CC3) stains in vehicle- and IRAK4i-treated moPDAC-old. Scale bars, 50 μm. (K) Quantification of CC3 stain in vehicle- and IRAK4i-treated moPDAC-old. Results show mean ± SEM. *, P < 0.05, Mann-Whitney test. (L) Number of diaphragm metastases of vehicle- and IRAK4i- treated moPDAC-old. Results show mean ± SEM. *, P < 0.05, Mann-Whitney test. (M) Tumour growth, as measured by ultrasound-based imaging, shown as ratio of tumour volumes at day 14 (d14) over tumour volumes at day -1 (d-1) of vehicle- and IRAK4i- moPDAC-old. Results show mean ± SEM. *, P < 0.05, Mann-Whitney test. (N) Body weight change in vehicle- and IRAK4i- moPDAC-old at day 14 compared to day -1. Results show mean ± SEM. *, P < 0.05, Mann-Whitney test. Body weight at endpoint was calculated by removing the tumour weight. (O) Number of diaphragm metastases of vehicle- and IRAK4i- treated moPDAC-young. Results show mean ± SEM. No significant difference was observed, as assessed by Mann-Whitney test. (P) Tumour growth, as measured by ultrasound-based imaging, shown as ratio of tumour volumes at day 14 (d14) over tumour volumes at day -1 (d-1) of vehicle- and IRAK4i- moPDAC-young. Results show mean ± SEM. No significant difference was observed, as assessed by Mann-Whitney test. (Q) Body weight change in vehicle- and IRAK4i- moPDAC-young at day 14 compared to day -1. Results show mean ± SEM. No significant difference was observed, as assessed by Mann-Whitney test. Body weight at endpoint was calculated by removing the tumour weight.
Article Snippet: Primary antibodies were anti-mouse αSMA (ab5694; Abcam; RRID:AB_2223021), anti-human αSMA (M0851, DAKO; RRID:AB_2223500), CC3 (9664; Cell signaling technologies; RRID:AB_2070042), IRAK4 (4363; Cell Signaling Technologies; RRID:AB 2126429), and p-IRAK4 (MAB2538; Abnova; RRID:AB_10555313).
Techniques: Staining, MANN-WHITNEY, Derivative Assay, Imaging
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