Fig 1: POLQ is significant for PDAC progression and overall survival. (A) Kaplan–Meier survival analysis for KC and qKC mice (KC mice, n = 20; qKC mice, n = 14; p = 0.02 by Mantel–Cox [log rank] test). (B) Representative images of pancreatic tumor from 19 week old KC mice (hematoxylin and eosin stain). (C) Representative images of pancreatic tumor from 52 week old qKC mice (hematoxylin and eosin stain; scale bars of enlarged images represent 100 µm). (D–H) Pathological photographs of metastatic PDAC in a representative qKC mouse. (D) Abdominal distention is noted, due to the accumulation of malignant ascites. (E) Primary PDAC in the pancreas (asterisk) and liver metastasis (black arrow). Tissue sample from the same mouse showing (F) multiple liver metastases and (G) lung metastasis marked with black arrowheads. (H) Histology of healthy liver and lung of wild-type mouse, and liver and lung metastases of qKC mouse. Scale bars represent 100 µm. (I) Kaplan–Meier survival analysis of TCGA PDA patients with low and high POLQ expression carrying KRAS wild-type or oncogenic KRAS (KRAS wild-type and lower POLQ expression, n = 20; KRAS wild-type and higher POLQ expression, n = 20; KRAS mutation and lower POLQ expression, n = 36; KRAS mutation and higher POLQ expression, n = 36; p value is indicated for comparison of patients with both KRAS mutation and higher or lower POLQ expression using the Mantel–Cox [log rank] test. Comparison of patient with both KRAS wild-type and higher or lower POLQ expression shows no statistical significance (p > 0.05).
Fig 2: Deletion of POLQ affects tumor progression and differentiation in established pancreatic ductal adenocarcinoma in vivo. (A) Representative pancreases from 1 M, 3 M, 4.5 M, 6 M, 9 M, and 12 M WT, qKO, KC, and qKC animals. (B) Histology of the pancreas from age-matched wild-type, qKO, KC, and qKC mice at 1, 3, 4.5, 6, 9, and 12 months old. Arrows indicate PanIN lesions (hematoxylin and eosin stain; scale bars represent 100 µm). (C) Percentage content of PanIN lesions and (D) their histologic progression in KC and qKC mice at the age of 1 month (KC, n = 14; qKC, n = 9), 3 months (KC, n = 14; qKC, n = 9), 4.5 months (KC, n = 10; qKC, n = 10), 6 months (KC, n = 9; qKC, n = 8), 9 months (KC, n = 5; qKC, n = 8), and 12 months (KC, n = 5; qKC, n = 4). Error bars represent mean ± SD; * p < 0.05, ** p < 0.01, (Student’s t-test). (E–G) Alcian blue staining was performed to visualize differentiation. (E) Mucin-rich PanINs lesions are depicted in blue, cytoplasm in light red, and nuclei in dark red. Representative images of the pancreas from age-matched KC and qKC mice at 1, 3, 4.5, 6, 9, and 12 months old are shown. Scale bars represent 100 µm. Histological score of (F) cytoplasm and (G) PanINs in pancreas of KC and qKC animals at the age of 1 month (KC, n = 14; qKC, n = 9), 3 months (KC, n = 14; qKC, n = 9), 4.5 months (KC, n = 10; qKC, n = 10), 6 months (KC, n = 9; qKC, n = 8), 9 months (KC, n = 5; qKC, n = 8), and 12 months (KC, n = 5; qKC, n = 4). Error bars represent mean ± SD; * p < 0.05, ** p < 0.01, *** p = 0.0001, **** p < 0.0001 (Student’s t-test).
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