Prognostic Significance of Neuroepithelial Transforming Protein 1 in Hepatocellular Carcinoma

Objective: Recent works have demonstrated that neuroepithelial transforming protein 1 (NET-1) gene expression is associated with proliferation, metastasis, and clinical stages of human hepatocellular carcinoma (HCC). To investigate its prognostic significance in HCC, which currently is unknown, the authors examined the correlation between NET-1 expression and prognosis in patients with HCC. Methods: Immunohistochemical staining was used to determine NET-1 expression level in 368 paired HCC and normal liver tissue (NLT) specimens. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of HCC. Results: Among 368 specimens of HCC, the positive rate of NET-1 protein expression in HCC tissues was 86.7% (319/368), and the increased NET-1 expression was correlated significantly with high Edmondson-Steiner grade (p = .02) and TNM stage (p = .01). The expression level of NET-1 in HCC tissues was associated with intrahepatic metastasis (p = .008) and portal vein infiltration (p = .007). HCC patients with the moderate-strong NET-1 positive expression had either poorer disease-free survival or poorer overall survival than patients with negative-low positive NET-1 expression (p= .001 and .002, respectively). A multivariate Cox regression analysis revealed that NET-1 protein expression (relative risk 5.8; p = .01) was an independent prognostic factor for patients with HCC. Conclusion: Taken together, our study suggests for the first time that NET-1 status may be a new predictor of survival for HCC patients and provides the rationale for developing a novel therapy of targeting NET-1 against this fatal malignancy.