The secreted frizzled-related proteins (sFRPs) are reported to be antagonists of a number of tumors. This study was designed to investigate the relationship of sFRP4 with aggressiveness of pituitary adenomas. Specimens were classified into three groups: normal control (n = 10), non-aggressive group (n = 42) and aggressive group (n = 26) according to preoperative magnetic resonance imaging (MRI)/computed tomography. sFRP4 were investigated by PCR, Western blotting, and immunohistochemistry (IHC). The methylation status of the sFRP4 promoter region was observed by MassArray. Cell culture and 5-aza-2-deoxycytidine treatment was performed to observe the relationship of downregulation of sFRP4 with methylation of the sFRP4 gene. PCR and Western blot results showed that sFRP4 expression was downregulated in aggressive pituitary adenomas, which was confirmed by IHC. Methylation of the sFRP4 promoter was increased in aggressive pituitary adenomas. And methylation of the sFRP4 promoter lead to downregulation of sFRP4 expression. sFRP4 expression is inversely related to the aggressiveness of pituitary adenomas, and act as a tumor suppressor.
