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

Lan Liu; Zhaoting Yang; Weidong Ni; Yanhua Xuan

doi:10.1016/j.yexmp.2018.02.004

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

Exp Mol Pathol. 2018 Apr;104(2):134-139. doi: 10.1016/j.yexmp.2018.02.004. Epub 2018 Feb 21.

Authors

Lan Liu¹, Zhaoting Yang², Weidong Ni², Yanhua Xuan³

Affiliations

¹ 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.
² 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.
³ 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. Electronic address: xuanyh1@ybu.edu.cn.

PMID: 29475036
DOI: 10.1016/j.yexmp.2018.02.004

Abstract

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.

Keywords: ADAMTS-6; Esophageal squamous cell carcinoma; Prognosis; Twist-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ADAMTS Proteins / metabolism*
Aged
Biomarkers, Tumor / metabolism
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / mortality*
Carcinoma, Squamous Cell / pathology
Esophageal Neoplasms / metabolism*
Esophageal Neoplasms / mortality*
Esophageal Neoplasms / pathology
Esophageal Squamous Cell Carcinoma
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Nuclear Proteins / metabolism
Prognosis
Twist-Related Protein 1 / metabolism

Substances

Biomarkers, Tumor
Nuclear Proteins
TWIST1 protein, human
Twist-Related Protein 1
ADAMTS Proteins
Adamts6 protein, human