Prognostic significance of FOXP1 as an oncogene in hepatocellular carcinoma

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).

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.

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.

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.