Title : Associations between tumor-infiltrating neutrophils and clinical outcomes in patients with hepatocellular carcinoma undergoing surgical resection: A single-center retrospective study
Abstract:
Background:
Neutrophils have been previously shown to be implicated in the pathogenesis of hepatocellular carcinoma and serve as a critical component of the tumor microenvironment. However, the exact relationship between tumor-infiltrating neutrophils and clinical outcomes for hepatocellular carcinoma undergoing surgical resection remains largely unexplored. The present study aimed to elucidate the association between tumor-infiltrating neutrophils and time to recurrence (TTR) in hepatocellular carcinoma undergoing curative resection.
Methods:
In this single-center, retrospective observational study between April 2021 and October 2023, immunohistochemical staining for CD66 (neutrophil biomarker), CD4 and CD8 (T cell biomarker) were performed in the specimens of hepatocellular carcinoma from 138 patients. Demographic, clinical and laboratory data were all collected. The primary endpoint TTR was defined as the time interval from surgical resection to recurrence of any causes. Multivariable Cox proportional hazard regression model was applied to assess the relationship between tumor-infiltrating neutrophils and TTR.
Results:
A higher CD66+ infiltrating neutrophils was significantly positively associated with increased CD8+ T cells (r=0.41, P=0.008). During a median follow-up of 29 (interquartile range 16-30) months, 49 (35.51%) reached the primary endpoint. Kaplan-Meier survival analysis showed that those with a higher CD66+ cell count had significantly lower TTR than those with a lower CD66+ count (P<0.01). Multivariable-adjusted Cox proportional hazard regression analysis indicated that a higher Barcelona Clinic Liver Cancer classification (HR=2.42, 95% CI 1.42-4.01), higher AFP>400ng/ml (HR=1.52, 95%CI 1,21-1.80) and increased neutrophil infiltration (HR=1.99, 95% CI 1.53-2.52) were independent risk factors for a shorter TTR.
Conclusion:
A higher tumor-infiltrating neutrophil is an independent and useful histologic predictor for unfavorable clinical outcomes in patients with resectable hepatocellular carcinoma.
Keywords: Tumor-infiltrating,neutrophils,hepatocellular,carcinoma,surgical resection