Decreased expression of the Nkx2.8 gene correlates with tumor progression and a poor prognosis in HCC cancer

BACKGROUND: Nkx2.8 (Nk2 homeobox 8) is a novel NK-2 gene family member that has been implicated in the progression of human cancer. Its role in the progression of HCC remains unknown. In this study, we investigated the expression levels and prognostic value of Nkx2.8 in hepatocellular carcinoma. METHODS: The expression of Nkx2.8 was determined by real-time quantitative RT-PCR (qRT-PCR) and immunochemistry in paired cancerous and non-cancerous tissues of 48 patients with HCC. The relationships between the Nkx2.8 expression levels, the clinicopathological characteristics and patient survival were analyzed. The effects of Nkx2.8 overexpression on cellular proliferation ability, including MTT and colony formation assays, were investigated. RESULTS: Nkx2.8 expression was significantly downregulated in HCC cancer tissues compared with adjacent non-cancerous tissues. Further immunohistochemical analysis showed low expression of Nkx2.8 in HCC cancer tissues, and the clinicopathological analysis showed that the Nkx2.8 mRNA and protein expression levels were significantly correlated with the TNM stage (p = 0.032; p = 0.026, respectively). Kaplan–Meier survival curves revealed that lower Nkx2.8 expression was associated with a poor overall survival in HCC patients (P = 0.00172). The overexpression of Nkx2.8 in HCC cell lines inhibits cell proliferation and colony formation. CONCLUSIONS: Our data indicated that Nkx2.8 plays important roles in the development and progression of HCC and might be a valuable prognostic biomarker and potential therapeutic target for HCC.