Abstract
Brain glioma is the most common primary intracranial tumor characterized by dismal prognosis and frequent recurrence, yet a real-time and reliable biological approach to monitor tumor response and progression is still lacking. Recently, few studies have reported that circulating tumor cells (CTCs) could be detected in glioblastoma multiform (GBM), providing the possibility of its application in brain glioma monitoring system. But its application limits still exist, because the detection rate of CTCs is still low and was exclusively limited to high- grade gliomas. Here, we adopted an advanced integrated cellular and molecular approach of SE-iFISH to detect CTCs in the peripheral blood (PB) of patients with 7 different subtypes of brain glioma, uncovering the direct evidences of glioma migration. We identified CTCs in the PB from 24 of 31 (77%) patients with glioma in all 7 subtypes. No statistical difference of CTC incidence and count was observed in different pathological subtypes or WHO grades of glioma. Clinical data revealed that CTCs, to some extent, was superior to MRI in monitoring the treatment response and differentiating radionecrosis from recurrence of glioma. Conclusively, CTCs is a common property of brain gliomas of various pathological subtypes, which has provided an ultimate paradox for the hypothesis “soil and seed”. It can be used to monitor the microenvironment of gliomas dynamically, which will be a meaningful complement to radiographic imaging.
Highlights
Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors [1].In spite of the currently multimodal treatments, including surgery, chemotherapy and radiotherapy, the expectancy of survival time of glioma is still dismal [2]
The results showed that chromosome 8 polyploidy cells generally existed in these 10 glioma specimens, compared to the results of control group
Considering the distinct internal environment of brain, Cushing and Bailey first proposed that glioma would never lead to extracranial metastases
Summary
In spite of the currently multimodal treatments, including surgery, chemotherapy and radiotherapy, the expectancy of survival time of glioma is still dismal [2]. The current standard for measuring the effects of treatment in gliomas is the application of the Response Assessment in NeuroOncology (RANO) criteria based on the radiological appearance of tumor on MRI [3]. There is an unresolved problem-radionecrosis, a treatment-related response of brain tissue to radiation, in the radiological presentation of glioma, which could mimic true tumor progression [4]. Liquid biopsy, a promising, noninvasive mean to evaluate the status of glioma, www.impactjournals.com/oncotarget. This misconception that brain glioma cells could never get into the blood, has been challenged in recent two years. In 2014, researchers have firstly found CTCs in the peripheral blood (PB) of patients with GBM, and declared that CTC is the “intrinsic property” of GBM biology [10]
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