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  • Differential Expression of Folate Receptor 1 in Medulloblastoma and Its Relationship to Clinicopathological Characteristics and Targeted Therapy

    Final Number:

    Hailong Liu; Qianwen Sun; Youliang Sun; Mingshan Zhang; Yanming Qu; Zhihua Zhang; Xinyi Fan; CJ Yu; Yongmei Song

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2017 Annual Meeting

    Introduction: Medulloblastoma is the most common malignant CNS tumor of childhood. High expression of folate receptor 1 (Folr1) was observed in some malignant epithelial tumors. However its expression and the role for clinicopathological significance and targeted therapeutic potential in MB still remain unclear.

    Methods: In current study we have detected the differential expression of Folr1 in MB specimens and cells and identified its clinical, pathological and radiological values to be considered as a biomarker for diagnosis of MB. Then we have studied the targeted treatment of MB with Folr 1 targeted cytarabine (Folr1-Ara-C) both in vitro and in vivo.

    Results: Folr1 protein and mRNA were overexpressed in MB specimens, while the expression level correlated with pathological subtypes. Folr1 expression was positively correlated with CSF spreading, Ki-67, MMP9, pathological subtypes and serum Folr1. Factors of age, CSF spreading, Ki-67, MMP9, strong Folr1 expression and pathological subtypes were found to be the independent prognostic values for patients with MB. Serum Folr1 presented increasing trends in turn with the different subgroups of MB, indicating that serum Folr1 showed rational sensitivity and specificity in demonstrating histological types. Folr1-Ara-C led to changes in cellular proliferation and invasion with down-regulation of MMPs proteins and activation of apoptosis in vitro. Using mouse xenograft models, Folr1-Ara-C suppressed tumor growth and improved survival of mouse by MRI and PET/CT. Immunohistochemical analysis of xenograft specimens showed decreased Ki-67 and MMP9 labelling index suggesting the effects on proliferation and invasion in vivo.

    Conclusions: Folr1 may be considered as a molecular predictive candidate for histological types and serum Folr1 may be a novel noninvasive biomarker for diagnosis of MB. The application of Folr1-Ara-C contributed to be one kind of targeted therapies for MB.

    Patient Care: Our research elucidated an important role for Folr1 expression in MB and unraveled a forward targeting Folr1 therapy for MB or other high-expressed cancers.

    Learning Objectives: To discover the differential expression of Folr1 in MB and its relationship to clinical, pathological and radiological features as well as targeted therapy for MB indicating that Folr1 could be used as a potential candidate to diagnose and treat.

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