Abstract

Current techniques for diagnosing glioma are invasive and do not accurately predict prognosis. We developed a novel, non-invasive liquid chip assay to diagnose glioma and predict prognosis. Using this method, we determined the methylation state of the Alu element in cell-free DNA extracted from the serum of 109 glioma patients. Controls included 56 patients with benign intracranial tumors and 50 healthy subjects. Matched tumor tissues were processed for 36 patients. The cfDNA from glioma patients showed lower levels of Alu methylation than the controls (P<0.01). Alu methylation was also lower in high-grade than low-grade gliomas (P<0.01), indicating that Alu methylation correlates negatively with disease severity. Moreover, Alu methylation correlated positively with survival (P<0.01). These findings suggest high-throughput liquid chip could serve as a non-invasive diagnostic assay for glioma.

Highlights

  • Gliomas are tumors arising from glial cells and account for almost 70% of primary malignant tumors in the central nervous system

  • Alu methylation levels in cell-free DNA (cfDNA) are lower for glioma patients than for both benign and healthy controls (P

  • To date, tumorderived cfDNA has been evaluated as a potential diagnostic tool for the detection of systemic cancer, making it an important method to diagnose gliomas by blood-based methods

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Summary

Introduction

Gliomas are tumors arising from glial cells and account for almost 70% of primary malignant tumors in the central nervous system. The initial diagnosis for gliomas includes neurologic symptoms and radiographic imaging using CT or MRI [1, 2]. Current imaging techniques do not contribute conclusive diagnostic information and cannot predict prognosis. The gold-standard to confirm initial diagnosis is a tissue biopsy, which can be problematic due to its highly-invasive nature. Given the highly fatal nature of glioma, early diagnosis is key to a positive prognosis. An accurate, efficient and non-invasive technique for early diagnosis is needed to improve the prognosis of glioma patients

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