Wei Jin1,2,3,4, Hua-Xiang Xu1,2,3,4, Shi-Rong Zhang1,2,3,4, Hao Li1,2,3,4, Wen-Quan Wang1,2,3,4, He-Li Gao1,2,3,4, Chun-Tao Wu1,2,3,4, Jin-Zhi Xu1,2,3,4, Zi-Hao Qi1,2,3,4, Shuo Li1,2,3,4, Quan-Xing Ni1,2,3,4, Liang Liu5,6,7,8, Xian-Jun Yu9,10,11,12. 1. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, People's Republic of China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. 3. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, People's Republic of China. 4. Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China. 5. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, People's Republic of China. liuliang@fudanpci.org. 6. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. liuliang@fudanpci.org. 7. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, People's Republic of China. liuliang@fudanpci.org. 8. Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China. liuliang@fudanpci.org. 9. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, People's Republic of China. yuxianjun@fudanpci.org. 10. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. yuxianjun@fudanpci.org. 11. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, People's Republic of China. yuxianjun@fudanpci.org. 12. Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China. yuxianjun@fudanpci.org.
Abstract
BACKGROUND: Tumor-infiltrating neutrophils (TINs) indicate poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC). Activated neutrophils can generate neutrophil extracellular traps (NETs). Little is known about the presence and prognostic significance of tumor-infiltrating NETs in PDAC. METHODS: This study enrolled 317 patients, in two independent sets (training and validation), who underwent curative pancreatectomy for PDAC in Shanghai Cancer Center. TINs and NETs were identified by immunohistochemical staining for CD15 and citrullinated histone H3, respectively. The relationship between clinicopathological features and outcomes was analyzed. Accuracy of prognostic prediction models was evaluated using concordance index (C-index) and Akaike information criterion (AIC). RESULTS: NETs were associated with OS (both, P < 0.001) and RFS (both, P < 0.001) in the training and validation sets. Tumor-infiltrating NETs predicted poor postsurgical survival of patients with PDAC. Moreover, multivariate analysis identified NETs and AJCC TNM stage as two independent prognostic factors for OS and RFS. Combination of NETs with the 8th edition TNM staging system (C-index, 0.6994 and 0.6669, respectively; AIC, 1067 and 1126, respectively) generated a novel model that improved the predictive accuracy for survival in both sets (C-index, 0.7254 and 0.7117, respectively; AIC, 1047 and 1102, respectively). The model combining presence of NETs with the 7th edition AJCC TNM staging system also had improved predictive accuracy. CONCLUSIONS: NETs were an independent prognostic factor in PDAC and incorporation of NETs along with the standard TNM stating system refined risk-stratification and predicted survival in PDAC with improved accuracy.
BACKGROUND:Tumor-infiltrating neutrophils (TINs) indicate poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC). Activated neutrophils can generate neutrophil extracellular traps (NETs). Little is known about the presence and prognostic significance of tumor-infiltrating NETs in PDAC. METHODS: This study enrolled 317 patients, in two independent sets (training and validation), who underwent curative pancreatectomy for PDAC in Shanghai Cancer Center. TINs and NETs were identified by immunohistochemical staining for CD15 and citrullinated histone H3, respectively. The relationship between clinicopathological features and outcomes was analyzed. Accuracy of prognostic prediction models was evaluated using concordance index (C-index) and Akaike information criterion (AIC). RESULTS: NETs were associated with OS (both, P < 0.001) and RFS (both, P < 0.001) in the training and validation sets. Tumor-infiltrating NETs predicted poor postsurgical survival of patients with PDAC. Moreover, multivariate analysis identified NETs and AJCC TNM stage as two independent prognostic factors for OS and RFS. Combination of NETs with the 8th edition TNM staging system (C-index, 0.6994 and 0.6669, respectively; AIC, 1067 and 1126, respectively) generated a novel model that improved the predictive accuracy for survival in both sets (C-index, 0.7254 and 0.7117, respectively; AIC, 1047 and 1102, respectively). The model combining presence of NETs with the 7th edition AJCC TNM staging system also had improved predictive accuracy. CONCLUSIONS: NETs were an independent prognostic factor in PDAC and incorporation of NETs along with the standard TNM stating system refined risk-stratification and predicted survival in PDAC with improved accuracy.
Authors: Roni F Rayes; Jack G Mouhanna; Ioana Nicolau; France Bourdeau; Betty Giannias; Simon Rousseau; Daniela Quail; Logan Walsh; Veena Sangwan; Nicholas Bertos; Jonathan Cools-Lartigue; Lorenzo E Ferri; Jonathan D Spicer Journal: JCI Insight Date: 2019-07-25
Authors: Clara S Mundry; Kirsten C Eberle; Pankaj K Singh; Michael A Hollingsworth; Kamiya Mehla Journal: Biochim Biophys Acta Rev Cancer Date: 2020-06-21 Impact factor: 10.680