Expression and prognostic significance of doublecortin-like kinase 1 in patients with hepatocellular carcinoma
Expression and prognostic significance of doublecortin-like kinase 1 in patients with hepatocellular carcinoma
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DOI：
10.3892/ol.2017.7082
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发表时间：
2017-12-01
期刊：
影响因子：
2.9
通讯作者：
Dai, Guanghai
中科院分区：
文献类型：
--
作者：
Fan, Mengjiao;Qian, Niansong;Dai, Guanghai
双皮质素样激酶1（DCLK 1）是肠和胰腺肿瘤中公认的癌症干细胞标志物，与肿瘤发病机制和进展以及许多类型癌症的不良生存结局相关。然而，在肝细胞癌（HCC）中DCLK 1的表达及其预后价值仍不清楚。在本研究中，DCLK 1的表达进行了评估，使用免疫组化在96切除HCC和68个相邻组织标本。染色强度和染色细胞百分比分别以0-3和0-4的量表评分。如果复合多重评分>3，则组织被定义为DCLK 1阳性。DCLK 1在肝癌和癌旁组织中均呈胞浆表达，表达率分别为81%（78/96）和74%（50/68）;中位评分分别为4.6和3.9，肝癌和癌旁组织间差异无统计学意义（P=0.087）。DCLK 1表达与肝内转移呈正相关（P=0.035）。单因素分析显示DCLK 1表达与无病生存期（DFS）和总生存期显著相关（P=0.024和0.034）。多因素分析显示DCLK 1表达是影响肝细胞癌DFS的独立预后因素（P=0.019;风险比1.546; 95%可信区间1.330-1.725）。分层Kaplan-Meier生存曲线显示DCLK 1表达预测门静脉转移、肝内转移和肝硬化三个特征阳性的DFS较差（分别为P=0.020、P=0.007和P=0.017）。总的来说，本研究的结果表明，DCLK 1，作为一种肿瘤促进剂，在HCC中经常过表达，并且DCLK 1表达与HCC患者的DFS较差相关。DCLK 1可能是肝癌治疗的一个有前途的靶点，需要进一步研究。
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.