ADAMTS-6 is a predictor of poor prognosis in patients with esophageal squamous cell carcinoma

作者:Liu, Lan; Yang, Zhaoting; Ni, Weidong; Xuan, Yanhua*
来源:Experimental and Molecular Pathology, 2018, 104(2): 134-139.
DOI:10.1016/j.yexmp.2018.02.004

摘要

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.