Fan Mengjiao, Qian Niansong, Dai Guanghai
Department of Oncology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
Oncol Lett. 2017 Dec;14(6):7529-7537. doi: 10.3892/ol.2017.7082. Epub 2017 Sep 27.
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.
双皮质素样激酶1（DCLK1）是肠道和胰腺肿瘤中一种假定的癌症干细胞标志物，与肿瘤发病机制和进展相关，并且在多种癌症类型中与较差的生存结果相关。然而，DCLK1在肝细胞癌（HCC）中的表达及其预后价值仍不清楚。在本研究中，采用免疫组织化学方法评估了96例手术切除的HCC组织和68例癌旁组织标本中DCLK1的表达情况。染色强度和染色细胞百分比分别按0 - 3分和0 - 4分进行评分。如果综合评分>3，则组织被定义为DCLK1阳性。在HCC组织和癌旁组织标本中均观察到DCLK1的细胞质表达，表达率分别为81%（78/96）和74%（50/68）；中位数评分分别为4.6和3.9，HCC组织与癌旁组织之间未观察到统计学显著差异（P = 0.087）。DCLK1表达与肝内转移呈正相关（P = 0.035）。此外，单因素分析显示DCLK1表达与无病生存期（DFS）和总生存期显著相关（P = 0.024和0.034）。多因素分析还表明，DCLK1表达是HCC患者DFS的独立预后因素（P = 0.019；风险比，1.546；95%置信区间，1.330 - 1.725）。分层的Kaplan - Meier生存曲线显示，DCLK1表达在门静脉转移、肝内转移和肝硬化这三个特征为阳性的情况下预测DFS较差（分别为P = 0.020、P = 0.007和P = 0.017）。总体而言，本研究结果表明，作为肿瘤促进因子的DCLK1在HCC中经常过度表达，并且DCLK1表达与HCC患者较差的DFS相关。DCLK1可能是HCC中一个有前景的治疗靶点，需要进一步研究。
