Fig. 7: Roles of Lfng in acinar- and ductal-derived pancreatic tumors in mice and association of LFNG expression with tumor grade and survival in human patients.
From: Lfng-expressing centroacinar cell is a unique cell-of-origin for p53 deficient pancreatic cancer
A, B Anti-GFP immunostaining in the pancreas of Lfng-eGFP;Kras;Mist1CreER/+ mice at 14 weeks post-tamoxifen injection. C, D Representative photomicrographs of pancreas from Kras;Mist1CreER/+ and Lfngfl/fl;Kras;Mist1CreER/+ mice at 12 weeks after tamoxifen injection. E Quantitation of ADM and PanIN lesions depicted in (C, D), presented as the percentage of total area affected by the precancerous lesions. **p < 0.01. F Anti-GFP immunostaining in the pancreas of Lfng-eGFP;p53fl/fl;Kras;Mist1CreER/+ mice at 7 weeks post-tamoxifen induction. G Kaplan-Meier survival analysis for p53fl/fl;Kras;Mist1CreER/+ and Lfngfl/fl;p53fl/fl;Kras;Mist1CreER/+ mice following tamoxifen injection at 1 month of age. Log-rank test p < 0.0001. H, I Anti-GFP immunostaining in the pancreas of Lfng-eGFP;p53fl/fl;Kras;Sox9-CreER mice 6 months after tamoxifen injection. J Anti-GFP immunostaining in the pancreas of Lfng-eGFP;p53fl/fl;Kras mice. K Kaplan-Meier survival analysis for p53fl/fl;Kras;Sox9-CreER and Lfngfl/fl;p53fl/fl;Kras;Sox9-CreER mice following tamoxifen injection at 1 month of age. Log-rank test p = 0.0246. L Genetic alterations of LFNG in patients with PDAC. M Overall survival of PDAC patients with or without LFNG alterations. Log-rank test p = 0.0182. Data derived from The Cancer Genome Atlas Program (TCGA) pancreatic cancer dataset. N, O Immunostaining for LFNG in tumor-adjacent near normal tissues from PDAC patients. Arrows: centroacinar cells. P–U Representative photomicrographs of anti-LFNG immunostaining on a human pancreatic tissue microarray containing specimens of adenocarcinoma (n = 38), acinic cell carcinoma (n = 1), and squamous cell carcinoma (n = 1), duplicate cores per case. ACC: acinic cell carcinoma. V Quantitation of LFNG immunostaining in adenocarcinomas of Grade 1, 2, and 3. Staining scores: 0 = completely negative, 1 = weak, 2 = intermediate, and 3 = strong. ANOVA p < 0.0001. Scale bars: 50 μm in (A–D, F, and H–J); 25 μm in (N, O); 100 μm in (P–U).
