ADAMTS-6 is a predictor of poor prognosis in patients with esophageal squamous cell carcinoma
ADAMTS-6 is a predictor of poor prognosis in patients with esophageal squamous cell carcinoma
复制标题
ADAMTS-6 是食管鳞状细胞癌患者预后不良的预测因子
DOI：
10.1016/j.yexmp.2018.02.004
复制
发表时间：
2018-04-01
影响因子：
3.6
通讯作者：
Xuan, Yanhua
中科院分区：
文献类型：
--
作者：
Liu, Lan;Yang, Zhaoting;Xuan, Yanhua
背景资料：具有血小板反应蛋白基序的去整合素和金属蛋白酶（ADAMTS）酶在细胞功能包括粘附、侵袭、迁移和增殖中起重要作用。ADAMTS-6是ADAMTS家族的一员;关于其与食管鳞状细胞癌（ESCC）进展关系的报道很少。方法：采用免疫组化（IHC）法检测171例食管鳞癌组织中ADAMTS-6的表达，并分析ADAMTS-6与食管鳞癌临床病理特征及Twist-1表达的关系。结果：ADAMTS-6主要表达于细胞质和细胞核，在肿瘤组织中的表达明显高于对照组。ADAMTS-6的表达与胃癌的临床分期（P = 0.009）、pT分期（P = 0.042）、淋巴结转移（P = 0.014）和复发（P = 0.033）有关。ADAMTS-6的表达与患者年龄、性别、肿瘤大小、远处转移、分化程度、肿瘤大小等临床病理参数无明显相关性。化疗、放疗、CD68表达和上皮间质转化（EMT）状态。Kaplan-Meier生存曲线显示ADAMTS-6表达上调提示OS（P = 0.001）和DFS（P = 0.002）缩短。多因素分析证实ADAMTS-6高表达是影响食管鳞癌预后的独立因素。ADAMTS-6与Twist-1在食管鳞癌细胞（P = 0.007）和间质细胞（P <0.001）中的表达呈显著相关。ADAMTS-6和Twist-1同时表达的ESCC患者的OS和DFS率明显低于其他患者。结论：ADAMTS-6高表达是ESCC患者预后不良的一个有用标志。
Background: A disintegrin and metalloprotease with thrombospondin motif (ADAMTS) enzymes play important roles in cell functions including adhesion, invasion, migration, and proliferation. ADAMTS-6 is a member of the ADAMTS family; reports of its relationship with esophageal squamous cell carcinoma (ESCC) progression are rare. It is unclear whether ADAMTS-6 could be an independent ESCC biomarker.Methods: ADAMTS-6 expression was detected by immunohistochemistry (IHC) in 171 paraffin-embedded ESCC specimens; relationships with patients' clinicopathological features and Twist-1 expression were analyzed by the Pearson Chi-square method, respectively. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method and compared using the long-rank test.Results: ADAMTS-6 was expressed mainly in the cytoplasm and nucleus; the expression was significantly higher in tumor tissues. Increased expression of ADAMTS-6 correlated with clinical stage (P = 0.009), pT stage (P = 0.042), lymph node metastasis (P = 0.014) and recurrence (P = 0.033). There were no significant correlations between ADAMTS-6 expression and other clinicopathological parameters including age, sex, tumor size, distant metastasis, differentiation, ... chemotherapy, radiotherapy, CD68 expression and epithelial mesenchymal transition (EMT) status. Kaplan-Meier survival curves revealed that upregulated expression of ADAMTS-6 indicated short OS (P = 0.001) and DFS (P = 0.002). Multivariate analysis confirmed that high ADAMTS-6 expression was an independent factor for ESCC prognosis. ADAMTS-6 expression was significantly correlated with Twist-1 expression in ESCC cancer cells (P = 0.007) and stromal cells (P < 0.001). Patients with ESCC revealing expression of both ADAMTS-6 and Twist-1 exhibited significantly reduced OS and DFS rates than other patients.Conclusions: High ADAMTS-6 expression is a useful marker of poor prognosis in patients with ESCC.