Preoperative leukocytosis is associated with increased tumor-infiltrating neutrophil extracellular traps and worse outcomes in esophageal cancer

Background: We evaluated the correlation between preoperative white blood cell (WBC) count and the prognosis in esophageal cancer (EC) patients who underwent esophagectomy, and explored the potential link between preoperative WBC count and tumor-infiltrating neutrophil extracellular traps (NETs) in EC. Methods: From January 2013 to December 2017, 3,096 patients at Fudan University Shanghai Cancer Center (FUSCC) undergoing esophagectomy for EC were enrolled in this retrospective cohort. The prognostic value of preoperative WBC count together with tumor-infiltrating NETs was investigated. Results: Leukocytosis (>= 10,000/mu L) was significantly associated with decreased overall survival (OS) and disease-free survival (DFS) (P<0.05). Further, moderate leukocytosis (>= 7,000/mu L) were also identified as an independent prognostic factor for survival. Additionally, moderate leukocytosis was correlated with male sex (P=0.006), advanced T stage (P<0.001), TNM stage (P<0.001) and ineffective postoperative chemotherapy (P<0.001), and moderate leukocytosis even predicted increased relapse postoperatively (P<0.001). Importantly, patients with moderate leukocytosis had a significantly higher level of intra-tumoral NETs infiltration (P<0.001), and the higher level of NETs infiltration were associated with worse OS and DFS (P<0.001). Conclusions: Our data indicated that preoperative moderate leukocytosis is associated with increased tumor-infiltrating NETs and is an independent prognostic factor for survival in EC after surgery.