Low SLC29A1 expression is associated with poor prognosis in patients with hepatocellular carcinoma.

ABSTRACT

Overall survival of patients with hepatocellular carcinoma (HCC) remains poor, and the multidrug resistance of HCC cells contributes to the limited efficacy of anti-cancer drugs, and reduced time to recurrence. We systematically screened the expression of transporter genes in HCC samples and found that solute carrier family 29 member A1 (SLC29A1) expression was significantly elevated in human HCC cells compared with para-carcinoma cell samples. The results of tissues microarray showed that SLC29A1 was an independent prognostic factor for overall survival and tumor recurrence, especially for patients with AFP ≤ 20 ng/ml, no microvascular invasion and early staging. In vivo and vitro analyses showed that down-regulation of SLC29A1 expression could enhance tumor cell proliferation, invasion and reduced drug sensitivity. Further microarray-based gene expression profile indicated that low SLC29A1 expression may contribute to HCC progression by promoting the epithelial-mesenchymal transition through zinc finger E-box binding homeobox 2 and transforming growth factor beta receptor activation, modifying cell adhesion through up- or down-regulation of cell adhesion molecules, and activating the nuclear factor-kappaB pathway through tripartite motif-containing protein 9 inhibition. In conclusion, low SLC29A1 expression correlated with high recurrence risk and poor outcomes for patients with HCC after surgery. SLC29A1 might be a promising prognostic factor, a potential tumor suppressor, and a drug sensitizer for patients with HCC through its interaction with various signaling pathways involved in this disease.