Epigenetic silencing of ADAMTS5 is associated with increased invasiveness and poor survival in patients with colorectal cancer

Abstract

Purpose

A disintegrin and metalloprotease with motif 5(ADAMTS5) has been involved in colorectal cancer (CRC) with hypermethylation in the promoter. However, its role in CRC remains unclear. The aim of this study was to explore the clinical significance and biological effect of ADAMTS5 on colorectal carcinogenesis. Through MSP, qRT-PCR, WB and IHC analysis, followed by a variety of in vitro assays, we report the function of ADAMTS5 in CRC. ADAMTS5 was markedly hypermethylaed and downregulated in tumor tissues compared with non-tumor tissues (p < 0.001). Negative expression of ADAMTS5 was much more common in tumor tissues than that in normal tissues (p < 0.001) and correlated with histologic types (p = 0.002), poor OS (p = 0.029) and DFS (p = 0.018). In vitro assay revealed that overexpression of ADAMTS5 inhibited the capabilities of migration and invasion of CRC cells, and no effect on cell growth, cell cycle and apoptosis. ADAMTS5 is hypermethylated and inhibits cancer cells invasion and migration in colorectal cancer, and correlates with OS and DFS, indicating that ADAMTS5 might be a useful biomarker in colorectal cancer therapy.

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