Fig. 1

Increased expression of interleukin-1 receptor antagonist is associated with malignant progression of PDA. (A) Left: Comparison of IL1RN mRNA level between PDA (T) and healthy pancreas (N). Expression data were analyzed from the PAAD dataset of The Cancer Genome Atlas (TCGA) (n = 182) and the normal pancreas dataset of GTExPortal (n = 328). TPM: transcript per million. Student’s t-test was performed. Right: Kaplan-Meier survival analysis between two groups of patients by a cut-off value of IL1RN mRNA expression (low IL1RN vs. high IL1RN). FPKM: fragments per kilobase of exons per million mapped fragments. Data were analyzed by Human Protein Atlas website. (B) Correlation analyses between IL1RN mRNA level and ten gene programs (GP1-GP10), which were assigned into four subtypes of PDA. Each gene program consists of a different number of signature genes (labeled in parenthesis). Correlation coefficients are visualized by a heat map. (C) Immunohistochemical (IHC) analysis using an antibody against IL-1Ra protein (gene name: IL1RN) (brown). Patient-derived xenografts (PDX#1-#2) were derived from patients with PDA. Scale: 30 μm. (D) IHC analyses of IL-1Ra (brown) and FOXP3 (green) using clinical tissues directly from a PDA patient (upper panel). An identical procedure was performed in tumor-adjacent normal pancreas from the same patient, showing epithelial cells of a pancreatic duct (arrow) (lower panel). Scale: 60 μm. (E) Monitoring human serum IL-1Ra levels by ELISA. Sera were collected from PDA patients (Tumor, n = 17) and healthy donors (Normal, n = 20) at Taipei Medical University Hospital (Taipei, Taiwan). Student’s t-test was performed. (F) Correlation analysis of serum IL-1Ra and CA19-9 in the PDA patients’ sera (n = 17). r: Pearson’s correlation coefficient. * p < 0.05. ** p < 0.01. **** p < 0.0001