Differential expression of folate receptor 1 in medulloblastoma and the correlation with clinicopathological characters and target therapeutic potential
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Hailong Liu1,2, Qianwen Sun3, Mingshan Zhang1, Zhihua Zhang1,2, Xinyi Fan2, Hongyu Yuan2, Cheng Li1, Yuduo Guo1, Weihai Ning1, Youliang Sun4, Yongmei Song2, Chunjiang Yu1
1Department of Neurosurgery, Sanbo Brain Hospital Capital Medical University, Beijing, P.R. China
2State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
3Department of Neurology, Qilu Hospital Shandong University, Jinan, P.R. China
4School of Basic Medical Science, Capital Medical University, Beijing, P.R. China
Chunjiang Yu, email: [email protected]
Yongmei Song, email: [email protected]
Keywords: medulloblastoma, folate receptor 1, prognosis, biomarker, therapeutic target
Received: November 22, 2016 Accepted: February 07, 2017 Published: February 18, 2017
Medulloblastoma is the most common malignant brain tumor in children. Folate receptor 1 (Folr1) was abundantly expressed in some epithelial malignancies. However the expression profile and the role of clinicopathological significance and therapeutic target potential in medulloblastoma still remain elusive. Currently we detected the expression of Folr1 in medulloblastoma and identified the diagnostic application by evaluating the clinical, pathological and neuroimaging values. Then we developed a target therapeutic compound with Folr1, which exhibited promising efficiency in treatment of medulloblastoma. Folr1 expression was up-regulated in medulloblastoma and positively correlated with percentage of Ki-67 and MMP9 labeling, pathological subtypes, serum Folr1 levels and CSF spreading on MRI. The level of serum Folr1 showed rational sensitivity and specificity in predicting histological subgroups. Strong Folr1 expression was recommended as the independent value regarding the prognosis of patients with medulloblastoma. Folr1 targeted therapy attenuated the tumor growth and metastasis with down-regulation of MMPs proteins and activation of apoptosis. Immunostaining analysis in the xenograft samples showed the decreased Ki-67 and MMP9 index providing the strong evidences that Folr1 targeted application can suppress the proliferation and invasion. Our findings uncovered in Folr1 a predictive candidate and therapeutic target for medulloblastoma.
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