Expression and prognostic significance of doublecortin-like kinase 1 in patients with hepatocellular carcinoma.

Doublecortin-like kinase 1 (DCLK1), a putative cancer stem cell marker in intestinal and pancreatic tumors, is associated with tumor pathogenesis and progression, and poor survival outcomes in numerous types of cancer. However, DCLK1 expression and its prognostic value remain unclear in hepatocellular carcinoma (HCC). In the present study, the expression of DCLK1 was assessed using immunohistochemistry in 96 resected HCC and 68 adjacent tissue specimens. The staining intensity and the percentage of stained cells were scored on a scale of 0-3 and 0-4, respectively. Tissue was defined as positive for DCLK1 if the composite multiple score was >3. Cytoplasmic expression of DCLK1 was observed in HCC and adjacent tissue specimens with an expression rate of 81% (78/96) and 74% (50/68), respectively; the median score was 4.6 and 3.9, respectively, and no statistically significant difference was observed between HCC and adjacent tissues (P=0.087). DCLK1 expression was positively associated with intrahepatic metastasis (P=0.035). Furthermore, univariate analysis revealed that DCLK1 expression was significantly associated with poor disease-free survival (DFS) and overall survival (P=0.024 and 0.034). Multivariate analysis also demonstrated that DCLK1 expression was an independent prognostic factor for DFS in HCC (P=0.019; hazard ratio, 1.546; 95% confidence interval, 1.330-1.725). Stratified Kaplan-Meier survival curves revealed that DCLK1 expression predicted poorer DFS with respect to positivity for three characteristics: Portal venous metastasis, intrahepatic metastasis, and cirrhosis (P=0.020, P=0.007 and P=0.017, respectively). Collectively, the results of the present study suggested that DCLK1, functioning as a tumor promoter, is frequently overexpressed in HCC, and that DCLK1 expression is associated with poor DFS in patients with HCC. DCLK1 may represent a promising therapeutic target in HCC and requires further study.