Prognostic significance of FOXP1 as an oncogene in hepatocellular carcinoma

Abstract

Background: Forkhead Box P1 (FOXP1) has been described as both a tumour suppressor candidate and a potential oncogene. The aim of this study is to identify new prognostic biomarkers and therapeutic target structures for the diagnosis and treatment of hepatocellular carcinoma (HCC).

Methods: The expression of FOXP1 mRNA in HCC was characterised using real-time PCR and 20 pairs of fresh frozen HCC tissues and corresponding non-cancerous tissues. FOXP1 protein expression in HCC was confirmed using immunohistochemistry on a tissue microarray chip. Finally, FOXP1 expression was correlated with conventional clinicopathological features of HCC and patient outcome.

Results: The expression of FOXP1 mRNA and protein in HCC cells was much higher than in normal hepatic cells (Z=2.315, p=0.021 and χ(2)=28.071, 95% CI 0.233 to 0.480, p<0.001, individually). The comparison of clinicopathological characteristics and immunohistochemistry by χ(2) test analysis showed that the high expression of FOXP1 in HCC was related to large tumour diameter (χ(2)=6.210, p=0.013), high serum α-fetoprotein levels (χ(2)=6.920, p=0.031) and later stage grouping with tumour node metastasis classification (χ(2)=6.714, p=0.035). Kaplan-Meier survival and Cox regression analysis showed that high FOXP1 expression (HR=2.182, 95% CI 1.146 to 4.154, p=0.018) and regional lymph node metastasis (HR=2.326, 95% CI 1.037 to 5.217, p=0.041) were independent prognosis factors.

Conclusions: From this investigation the authors elucidated for the first time that the correlation of high FOXP1 expression correlates with an aggressive malignant phenotype and may constitute a novel prognostic factor for HCC. These results also support a role for FOXP1 as an oncogene in HCC.