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

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Acknowledgments

This work was supported by grants from the National Science Foundation for Distinguished Young Scholars of China (81625016), the National Natural Science Foundation of China (81472670, 81871941, 81872366, 81802380, and 81802675), the Outstanding Academic Leader Program of the “Technological Innovation Action Plan” in Shanghai Science and Technology Commission (18XD1401200), and the Young Talented Specialist Training Program of Shanghai.

Author information

Author notes

  1. Wei Jin, Hua-Xiang Xu, Shi-Rong Zhang, and Hao Li contributed equally to this work.

Authors and Affiliations

  1. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, People’s Republic of China

    Wei Jin PhD, Hua-Xiang Xu MD, PhD, Shi-Rong Zhang M.Med, Hao Li MD, PhD, Wen-Quan Wang MD, PhD, He-Li Gao MD, PhD, Chun-Tao Wu MD, Jin-Zhi Xu M.Med, Zi-Hao Qi MD, Shuo Li MD, Quan-Xing Ni MD, Liang Liu MD, PhD & Xian-Jun Yu MD, PhD

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

    Wei Jin PhD, Hua-Xiang Xu MD, PhD, Shi-Rong Zhang M.Med, Hao Li MD, PhD, Wen-Quan Wang MD, PhD, He-Li Gao MD, PhD, Chun-Tao Wu MD, Jin-Zhi Xu M.Med, Zi-Hao Qi MD, Shuo Li MD, Quan-Xing Ni MD, Liang Liu MD, PhD & Xian-Jun Yu MD, PhD

  3. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, People’s Republic of China

    Wei Jin PhD, Hua-Xiang Xu MD, PhD, Shi-Rong Zhang M.Med, Hao Li MD, PhD, Wen-Quan Wang MD, PhD, He-Li Gao MD, PhD, Chun-Tao Wu MD, Jin-Zhi Xu M.Med, Zi-Hao Qi MD, Shuo Li MD, Quan-Xing Ni MD, Liang Liu MD, PhD & Xian-Jun Yu MD, PhD

  4. Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China

    Wei Jin PhD, Hua-Xiang Xu MD, PhD, Shi-Rong Zhang M.Med, Hao Li MD, PhD, Wen-Quan Wang MD, PhD, He-Li Gao MD, PhD, Chun-Tao Wu MD, Jin-Zhi Xu M.Med, Zi-Hao Qi MD, Shuo Li MD, Quan-Xing Ni MD, Liang Liu MD, PhD & Xian-Jun Yu MD, PhD

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  1. Wei Jin PhD
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  2. Hua-Xiang Xu MD, PhD
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Correspondence to Liang Liu MD, PhD or Xian-Jun Yu MD, PhD.

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Jin, W., Xu, HX., Zhang, SR. et al. Tumor-Infiltrating NETs Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 26, 635–643 (2019). https://doi.org/10.1245/s10434-018-6941-4

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