title: Assessment of sFRP4 as a bio-marker for predicting aggressiveness and recurrence of growth hormone-secreting pituitary adenomas.
abstract: The association of sFRP4 expression with aggressiveness and recurrence of growth hormone (GH)-secreting pituitary adenomas was investigated. Ten normal pituitary and 52 GH-secreting pituitary adenoma specimens were classified into three groups: normal pituitary (control) group, non-aggressive group, and aggressive group, according to preoperative evaluation by magnetic resonance imaging (MRI)/computed tomography (CT). Expression of sFRP4 was determined by quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, and tissue microarrays, to assess the association between sFRP4 and aggressiveness. Follow-up information of all 52 patients was collected to evaluate the impact of sFRP4 expression on the recurrence/progression of GH-secreting pituitary adenomas. qRT-PCR results showed a lower level of sFRP4 mRNA in the aggressive group, as compared to that in the non-aggressive group (P=0.001). A similar trend was observed on western blot analysis for sFRP4 protein expression (P=0.004). On analysis by tissue microarrays, weak sFRP4 expression was detected in the aggressive group (10/15, 66.7%). Univariate analysis showed a significant relationship between low sFRP4 expression and aggressiveness (P=0.024). On multivariate analysis weak sFRP4 expression was found to be an independent factor of recurrence/progression (odds ratio: 0.063, P=0.026). Methylation of the sFRP4 promoter was increased in low sFRP4 staining group compared to that in the high sFRP4 staining group (P<0.001). In this study, weak sFRP4 expression appeared to predict aggressive behavior, and was associated with recurrence/progression of GH-secreting pituitary adenomas. Methylation of the sFRP4 promoter may account for the low sFRP4 expression.
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Dongcheng, Beijing 100050, P.R. China.
authors.forename: Youtu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Dongcheng, Beijing 100050, P.R. China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Liu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Dongcheng, Beijing 100050, P.R. China.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Dongcheng, Beijing 100050, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.affiliation: Neurosurgical Department, Beijing Tiantan Hospital, Capital Medical University, Dongcheng, Beijing 100050, P.R. China.
authors.forename: Zhenye
authors.initials: Z
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Dongcheng, Beijing 100050, P.R. China.
authors.forename: Chuzhong
authors.initials: C
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Dongcheng, Beijing 100050, P.R. China.
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D014408:Biomarkers, Tumor; D019382:Human Growth Hormone; D011518:Proto-Oncogene Proteins; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins