The roles of sFRP4 and WIF1 in invasion and recurrence of non-functioning pituitary adenomas

Objectives To study the levels of secreted frizzled related protein 4 (sFRP4) and WNT inhibitory factor 1 (WIF1) in non-functioning pituitary adenomas (NFPAs) and to analyze their association with clinicopathologic features and the possibility as therapeutic targets. Methods A total of 126 specimens were obtained from Department of Neurosurgery of Beijing Tiantan Hospital, Capital Medical University from January 2012 to December 2016. The tissue microarray was constructed using 6 normal pituitary, Samples 54 invasive NFPAs and 72 non-invasive NFPAs samples. Immunochemistry staining (IHC) was used to measure the protein levels of WIF1 and sFRP4. Real-time PCR (RT-PCR) was detected for the mRNA levels of WIF1 and sFRP4 in GT1-1 cell. Cell proliferation experiment was used for cell viability of GT1-1 cell, and Transwell migration assay was used to measure the invasion ability of GH1-1 cells following decitabine treatment. Results H-Scores of sFRP4 and WIF in the invasive group were 134.5±45.3 and 73.7±24.1, and 223.3±47.6 and 133.6±35.7 in the non-invasive group according to the IHC experiment (P<0.05). Univariate analysis showed a significant correlation between tumor recurrence and either sFRP4 (r=-0.383, P=0.025) or WIF1 (r=-0.557, P=0.006). Compared with control GT1-1 cell (equal volume of dimethyl sulfoxide), the cell viability values were 84.5%±7.3%, 74.3%±6.5% and 62.2%±5.8% at 24 h, 48 h and 72 h post decitabine treatment. The trans-membrane positive cells were reduced to 154±42 after decitabine treatment, and those were 436±85 in the control group (P<0.01). The mRNA levels of sFRP4 and WIF1 were gradually increased with time after decitabine treatment (P<0.05). Conclusions The sFRP4 and WIF1 levels are closely related to the invasive behavior and recurrence of NFPAs. Decitabine could upregulate sFRP4 and WIF1 levels to inhibit the cell proliferation in GT1-1 cells. Key words: Pituitary neoplasms; Neoplasm invasiveness; Secreted frizzled-related protein 4; WNT inhibitory factor 1; Decitabine