Key Laboratory of Natural Resources of the Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University College of Medicine, Yanji 13302, China; Department of Pathology, Affiliated Hospital of Yanbian University, Yanji 133002, China.
Key Laboratory of Natural Resources of the Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University College of Medicine, Yanji 13302, China; Department of Pathology, Yanbian University College of Medicine, Yanji 13302, China.
Exp Mol Pathol. 2018 Apr;104(2):134-139. doi: 10.1016/j.yexmp.2018.02.004. Epub 2018 Feb 21.
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.
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.
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.
High ADAMTS-6 expression is a useful marker of poor prognosis in patients with ESCC.
解整合素和金属蛋白酶与血栓反应蛋白基序（ADAMTS）酶在细胞功能中发挥重要作用，包括粘附、侵袭、迁移和增殖。ADAMTS-6 是 ADAMTS 家族的成员；关于其与食管鳞状细胞癌（ESCC）进展的关系的报道很少。尚不清楚 ADAMTS-6 是否可以作为 ESCC 的独立生物标志物。
采用免疫组织化学（IHC）法检测 171 例石蜡包埋 ESCC 标本中 ADAMTS-6 的表达；采用 Pearson Chi-square 法分别分析 ADAMTS-6 与患者临床病理特征和 Twist-1 表达的关系。采用 Kaplan-Meier 法确定总生存期（OS）和无病生存期（DFS），并采用 Long-rank 检验进行比较。
ADAMTS-6 主要表达于细胞质和细胞核中；在肿瘤组织中的表达显著升高。ADAMTS-6 的表达增加与临床分期（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 表达与其他临床病理参数如年龄、性别、肿瘤大小、远处转移、分化、化疗、放疗、CD68 表达和上皮间质转化（EMT）状态无显著相关性。Kaplan-Meier 生存曲线显示，ADAMTS-6 表达上调预示 OS（P=0.001）和 DFS（P=0.002）较短。多因素分析证实，ADAMTS-6 高表达是 ESCC 预后的独立因素。ADAMTS-6 表达与 ESCC 癌细胞（P=0.007）和基质细胞（P<0.001）中的 Twist-1 表达显著相关。同时表达 ADAMTS-6 和 Twist-1 的 ESCC 患者的 OS 和 DFS 率明显低于其他患者。
ADAMTS-6 高表达是 ESCC 患者预后不良的有用标志物。
