Delta-like 1 homologue (DLK1) predicts clinical outcomes in patients with hepatocellular carcinoma

BACKGROUND: and purpose: Delta-like 1 homologue (DLK1), a transmembrane and secreted protein, is a non-canonical Notch ligand. DLK1 is also a hepatic stem/progenitor cell marker in both fetal liver and hepatocellular carcinoma (HCC). However, the role of DLK1 in HCC remains incompletely characterized. METHODS: We examined DLK1 expression patterns in 90 HCC specimens and paired adjacent non-tumorous liver tissues after surgical resection by using immunoblot analysis, and investigated their associations with clinicopathological parameters. The oncogenic functions of DLK1 were also analyzed in vitro. RESULTS: DLK1 protein levels were significantly upregulated in HCC tissues compared to adjacent normal liver tissues in about 36/90 (40 %) of patients, and high DLK1 expression in tumor was associated with shorter overall and disease-free survivals. Moreover, DLK1 expression in HCC tissues positively correlated with advanced BCLC stages and big tumor sizes. Subsequent in vitro experiments demonstrated that recombinant DLK1 (rDLK1) protein, markedly promoted the proliferation of hepatoma cells. Furthermore, genetic manipulation of cellular DLK1 levels regulates the proliferation and colonies formation of HCC cells in vitro. CONCLUSION: Our findings suggest that elevated DLK1 expression in HCC is linked to advanced BCLC stages, big tumor sizes and poor prognosis in HCC patients after surgical resection. DLK1 seems to serve as a valuable biomarker and may be a candidate for therapeutic targeting of HCC pending further validation.