Background: Previous studies suggest S100A9 is a promising biomarker for prognosis in cancer, including hepatocellular carcinoma (HCC). We examined the utility of serum S100A9 in predicting prognosis in HCC after curative resection.

Methods: We conducted a retrospective study of 379 HCC patients who underwent curative resection. Patients were randomly stratified into two independent groups to evaluate the prognostic value of S100A9. S100A9 was determined by ELISA.

Results: Patients with advanced disease showed significantly higher S100A9 levels (all P< 0.050). Serum S100A9 was elevated in patients who developed recurrence and death in both training and validation cohorts (all P< 0.050). In the training cohort, patients with higher preoperative S100A9 had a significantly shorter time to recurrence (15.50 vs. 64.00 months, P< 0.001) and decreased overall survival (34.80 months vs. not reached, P< 0.001). Cox regression demonstrated S100A9 was an independent indicator for poor prognosis after resection (both P< 0.050). These results were confirmed by the independent validation cohort.

Conclusions: Serum S100A9 is associated with dismal outcomes in HCC patients and can serve as a novel prognostic indicator for HCC patients after resection. Determination of S100A9 might help tailor treatment strategy to improve HCC patient prognosis.