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29.10.2018 | Pancreatic Tumors | Ausgabe 2/2019

Annals of Surgical Oncology 2/2019

Tumor-Infiltrating NETs Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 2/2019
Autoren:
PhD Wei Jin, MD, PhD Hua-Xiang Xu, M.Med Shi-Rong Zhang, MD, PhD Hao Li, MD, PhD Wen-Quan Wang, MD, PhD He-Li Gao, MD Chun-Tao Wu, M.Med Jin-Zhi Xu, MD Zi-Hao Qi, MD Shuo Li, MD Quan-Xing Ni, MD, PhD Liang Liu, MD, PhD Xian-Jun Yu
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1245/​s10434-018-6941-4) contains supplementary material, which is available to authorized users.
Wei Jin, Hua-Xiang Xu, Shi-Rong Zhang, and Hao Li contributed equally to this work.

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.

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