Stem cell factor is a novel independent prognostic biomarker for hepatocellular carcinoma after curative resection

Stem cell factor (SCF), a ligand of c-kit, is a hematopoietic growth factor. Uncontrolled activity of SCF/c-kit signaling pathway contributes to the formation of a variety of human malignancies. In this study, we determined whether SCF expression could risk-stratify patients with hepatocellular carcinoma (HCC) after curative resection. HCC tissues from 160 patients were collected during curative resection and stained with SCF and CD34, a marker for microvessel density (MVD), using immunohistochemistry. Two statistical analyses were performed: an independent continuous and a multivariate categorical analysis, with test/validation set-defined cut points, and Kaplan-Meier estimated outcome measures of overall survival (OS) and relapse-free survival (RFS). We found that higher levels of SCF confer worse OS (continuous P = 0.014; and categorical P = 0.009), and RFS (continuous P = 0.002; categorical P = 0.003) of patients with HCC. SCF varies independently from MVD-CD34, tumor node metastasis, histologic grade, age and gender, and retains prognostic significance when analysed as a categorical variable in a multivariate analysis. We confirmed that MVD-CD34 is also an independent prognostic marker for patients with HCC. The levels of SCF and CD34 showed a positive and significant correlation (P < 0.0001) and double low expression confers superior OS (median = 48 months) and RFS (median = 24 months), whereas double high expression confers shortest RFS (median = 10.5 months) compared with single measurements. The prognostic values of SCF and CD34 were independently determined in this study and we propose that both of them are independent prognostic markers for HCC.