The expression of ADAMTS14 is regulated by promoter DNA methylation and is associated with poor prognosis in colorectal cancer

Colorectal cancer (CRC) is one of the most common malignant tumors of digestive system, and its main cause of death is tumor metastasis. The occurrence of CRC is a polygenic and multi-step complex process involving genetic and epigenetic alterations. It has been demonstrated that ADAMTS14 (A disintegrin and metalloproteinase with thrombospondin motifs 14) was hypermethylated in esophageal cancer using whole-genome methylation microarray in our previous report. The present study revealed that ADAMTS14 was highly methylated accompanied with low expression in CRC. In addition, demethylation agent 5-Aza-dC could demethylate ADAMTS14 promoter region and reactivate ADAMTS14 expression effectively in vitro. Therefore, promoter hypermethylation was probably contributed to ADAMTS14 epigenetic silencing in CRC. Furthermore, ADAMTS14 protein expression was higher at invasive tumor front than at the tumor center or other areas of tumor. Kaplan-meier survival analysis indicated that the high ADAMTS14 expression was correlated with poor prognosis in CRC patients, suggesting the possibility that ADAMTS14 is a promising indicator in the evaluation of CRC prognosis.