Decreased expression of BATF2 is associated with a poor prognosis in hepatocellular carcinoma

Human BATF2, a basic leucine zipper protein, was recently detected in several normal immortalized cell lines but not in transformed cell lines. In addition, the expression of BATF2 also slowed the growth rate of malignant tumor cells injected into athymic nude mice. In this study, to study the role of BATF2 in hepatocellular carcinoma (HCC), we examined BATF2 expression in 50 paired HCC tumorous and nontumorous tissues, as well as in five HCC cell lines. Moreover, BATF2 expression in 114 HCC patients was evaluated using immunohistochemistry, and its relationship with clinicopathological parameters and prognosis was investigated. We found that BATF2 expression was significantly reduced in most HCC tumorous tissues, when compared with nontumorous tissues, as well as in the five HCC cell lines. Consistent with these results, the immunohistochemistry revealed that decreased BATF2 expression was present in 63 of the 114 cases and was significantly correlated with age (p = 0.006), tumor size (p = 0.046) and tumor differentiation (p = 0.030). Patients with negative BATF2 expression showed a shorter survival than those with positive expression (p = 0.016). Multivariate analysis revealed that BATF2 expression was an independent predictor of overall survival (p = 0.015). All the data support the hypothesis that BATF2 plays an important role in the progression of HCC and that it may work as a candidate tumor suppressor and a prognostic marker as well as a potential target for treatment.