Deletion at Dickkopf (Dkk)-3 Locus (11p15.2) Is Related With Lower Lymph Node Metastasis and Better Prognosis in Head and Neck Squamous Cell Carcinomas
Deletion at Dickkopf (Dkk)-3 Locus (11p15.2) Is Related With Lower Lymph Node Metastasis and Better Prognosis in Head and Neck Squamous Cell Carcinomas
复制标题
DOI：
10.3727/096504008786991594
复制
发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Nagatsuka, Hitoshi
中科院分区：
文献类型：
--
作者：
Katase, Naoki;Gunduz, Mehmet;Nagatsuka, Hitoshi
头颈部鳞状细胞癌（HNSCC）是一种多发病的癌症，尽管其治疗方法有所改进，包括化疗、放疗和手术，但生存率的提高仍然很差。人类肿瘤分子生物学的最新进展表明，HNSCC中存在多种分子异常，包括癌基因的激活和肿瘤抑制基因（TSGs）的失活。Dickkopf (Dkk)-3基因被认为是Writ信号的负调控因子，并被认为在多种恶性肿瘤中发挥TSG的作用。我们假设Dkk-3也可能在HNSCC中发挥重要作用。因此，在本研究中，我们通过杂合缺失（LOH）分析了Dkk-3位点（染色体11p15.2）的等位基因变异。研究人群包括50例HNSCC患者（平均年龄65岁）。此外，我们还研究了Dkk-3位点的LOH结果与临床病理参数之间的相关性，以研究其作为HNSCC生物标志物的用途。在研究的病例中检测到显著的LOH比率（57%），这表明Dkk-3可能参与了HNSCC的癌变。然而，有趣的是，与预期相反，我们发现Dkk-3位点LOH组的淋巴结转移较少，在生存分析中，与Dkk-3区域保留的患者相比，总生存率更高。这些结果表明，Dkk-3可能在HNSCC的癌变中发挥作用，但机制未知。此外，Dkk-3位点的等位基因缺失也可能作为HNSCC的一种新的预后生物标志物。
Head and neck squamous cell carcinoma (HNSCC) is a frequently occurring cancer, and despite improvement of its treatment methods, including chemotherapy, radiotherapy, and surgery, the improvement of survival remains poor. Recent advances in molecular biology of human cancer indicated various molecular abnormalities in HNSCC, including activation of oncogenes and inactivation of tumor suppressor genes (TSGs). Dickkopf (Dkk)-3 gene is known as a negative regulator of Writ signaling and is suggested to function as TSG in several kinds of malignancies. We hypothesized that Dkk-3 might play an important role in HNSCC, too. Thus, in the current study, we analyzed allelic alteration of Dkk-3 locus (chromosome 11p15.2) by means of loss of heterozygosity (LOH) analysis. The study population consisted of 50 patients with HNSCC (mean age of 65 years old). Furthermore, we also examined the correlation between LOH findings of Dkk-3 locus with clinicopathological parameters to investigate its use as a biomarker in HNSCC. A remarkable LOH ratio (57%) was detected in the cases studied, implying that Dkk-3 is likely to be involved in HNSCC carcinogenesis. However, interestingly and in contrast to the expectations, we found that the group with LOH of Dkk-3 locus had less lymph node metastasis, and showed a favorable overall survival compared to the patients with retention of Dkk-3 area in survival analysis. These results indicate that Dkk-3 can play a role in HNSCC carcinogenesis with unknown mechanism. Moreover, allelic loss at Dkk-3 locus may also be used as a novel prognostic biomarker in HNSCC.