Increased Cdc7 expression is a marker of oral squamous cell carcinoma and overexpression of Cdc7 contributes to the resistance to DNA-damaging agents
Increased Cdc7 expression is a marker of oral squamous cell carcinoma and overexpression of Cdc7 contributes to the resistance to DNA-damaging agents
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DOI：
10.1016/j.canlet.2013.05.008
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发表时间：
2013-09-01
期刊：
影响因子：
9.7
通讯作者：
Lee, Alan Yueh-Luen
中科院分区：
文献类型：
--
作者：
Cheng, An Ning;Jiang, Shih Sheng;Lee, Alan Yueh-Luen
Cdc 7-Dbf 4激酶（Dbf 4-dependent kinase，DDK）是DNA复制和DNA损伤反应（DNA damage response，DDR）的重要因子，与肿瘤的发生密切相关。然而，Cdc 7的表达从来没有与口腔鳞状细胞癌（OSCC）患者的结果，和Cdc 7介导的癌细胞存活的机制仍然不清楚。采用免疫组化法检测105例口腔鳞癌组织和30例口腔良性组织中Cdc 7蛋白的表达。采用Kaplan-Meier估计和对数秩检验对80例OSCC患者的总生存率进行了测量。通过腺病毒系统的Cdc 7过表达被用于仔细检查在DDR时促成癌细胞存活的潜在机制。计算机模拟分析表明，Cdc 7增加是癌症的共同特征。105例OSCC患者中96例（91.4%）Cdc 7过表达。Cdc 7表达较高的患者，分为两组：Cdc 7高表达（2+至3+）与Cdc 7低表达（0至1+）[风险比（HR）= 2.6; 95%置信区间（CI）128-5.43; P=0.0087]或四组（0至3+）[HR = 1.71; 95% CI = 1.20-2.44; P = 0.0032]，结果较差。多因素分析显示Cdc 7是一个独立的生存预测指标。过表达的Cdc 7抑制基因毒素诱导的细胞凋亡以增加癌细胞的存活。总之，Cdc 7的表达，这是普遍上调的癌症，是一个独立的预后标志物的口腔鳞癌。Cdc 7抑制基因毒素诱导的细胞凋亡，并增加DDR后癌细胞的存活率，表明Cdc 7的高表达增强了对化疗的抗性。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Cdc7-Dbf4 kinase (Dbf4-dependent kinase, DDK) is an essential factor of DNA replication and DNA damage response (DDR), which is associated with tumorigenesis. However, Cdc7 expression has never been associated to the outcome of oral squamous cell carcinoma (OSCC) patients, and the mechanism underlying cancer cell survival mediated by Cdc7 remains unclear. The Cdc7 protein expression of 105 OSCC tumor and 30 benign tissues was examined by immunohistochemisty assay. Overall survival rates of 80 OSCC patients were measured using Kaplan-Meier estimates and the log-rank tests. Cdc7 overexpression by adenovirus system was used to scrutinize the underlying mechanism contributed to cancer cell survival upon DDR. In silico analysis showed that increased Cdc7 is a common feature of cancer. Cdc7 overexpression was found in 96 of 105 (91.4%) studied cases of OSCC patients. Patients with higher Cdc7 expression, either categorized into two groups: Cdc7 high expression (2+ to 3+) versus Cdc7 low expression (0 to 1+) [hazard ratios (HR) = 2.6; 95% confidence interval (CI) 128-5.43; P=0.0087] or four groups (0 to 3+) [HR = 1.71; 95% CI = 1.20-2.44; P = 0.0032], exhibited a poorer outcome. Multivariate analysis showed that Cdc7 is an independent marker for survival prediction. Overexpressed Cdc7 inhibits genotoxin-induced apoptosis to increase the survival of cancer cells. In summary, Cdc7 expression, which is universally upregulated in cancer, is an independent prognostic marker of OSCC. Cdc7 inhibits genotoxin-induced apoptosis and increases survival in cancer cells upon DDR, suggesting that high expression of Cdc7 enhances the resistance to chemotherapy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.