Expression And Prognostic Significance Of Doublecortin-like Kinase 1 In Patients With Hepatocellular Carcinoma

Background and purpose: Doublecortin-like kinase 1 (DCLK1, formerly known as DCAMKL-1), a putative cancer stem cell marker in intestinal and pancreatic tumors, is known to be involved in tumor pathogenesis and progression. DCLK1 has been already investigated in many types of cancer and correlated with poor survival outcome.However, DCLK1 expression and its prognostic value remain unclear in hepatocellular carcinoma (HCC).Methods: In the present study, the expression of DCLK1 was analyzed by immunohistochemistry performed on 96 resected HCC tissue specimens, 53 liver cirrhosis specimens, and 15 non-cirrhosis liver specimens. The staining intensity and the amount of stained cells involved were scored on a scale of 0-3 and 0-4. Tissue was defined as positive (+) for DCLK1 if the composite multiple score was >3.Results: Cytoplasmic expression of DCLK1 was observed in HCC tissue specimens.The positive expression rate was 81% (78/96). The staining of HCC and liver cirrhosis was significantly higher than the non-cirrhosis tissues (P<0.05). However, no statistically significant was observed between HCCs and liver cirrhosis tissue. DCLK1 positive (+)expression was positively correlated with intrahepatic metastasis (+) (P=0.035).Furthermore, univariate analysis revealed that DCLK1 (+) expression status was significantly associated with poor prognostic outcome. Multivariate analysis further demonstrated that DCLK1 (+) was an independent prognostic factor for disease-free survival (DFS) of HCC (P=0.019). Stratified Kaplan-Meier survival curves revealed that DCLK1 (+) expression effectively predicted poorer DFS in three groups: portal venous metastasis (+), intrahepatic metastasis (+) and cirrhosis (+) subgroup patients (P=0.020,0.007 and 0.017, respectively).Conclusion: collectively, our data demonstrate that DCLK1 functioning as a tumor promotor is frequently overexpressed in HCC, and DCLK1 (+) expression level is associated with poor DFS in HCC patients. DCLK1 may be a promising therapeutic target in HCC, but still need to be further investigated.