Nerve growth factor expression in astrocytoma and cerebrospinal fluid: A new biomarker for prognosis of astrocytoma

Abstract

Background Recent studies have discovered that nuclear translocation of nerve growth factor (NGF) and its receptor fragments function differently from the traditional model. This study aimed to uncover the nuclear expression of NGF in astrocytoma and its biological significance. Methods Ninety-four paraffin-embedded astrocytoma specimens were subjected to immunohistochemical (IHC) and hemotoxylin & eosin (HE) staining. Preoperative cerebrospinal fluid (CSF) specimens and intraoperative snap-frozen astrocytoma tissues were assayed for NGF expression by ELISA and Western blotting. The outcome of patients who contributed samples was tracked. Each ten tissue samples from patients with traumatic brain injury who had received decompression surgery and CSF samples from patients undergoing spinal anesthesia but with no history of nervous system disease were taken as control. Results NGF-positive immunoreactive products were distributed in both the cytoplasm and nucleus of astrocytoma, but were only located in the cytoplasm of traumatic brain injury (TBI) tissue. NGF nuclear-positive rate (NPR) of grades III-IV astrocytomas (70.0%) was higher than that of grades I-II astrocytoma (28.6%, P <0.05). NGF-NP expression positively correlated with the NGF concentration in cerebrospinal fluid (CSF) (r=0.755, P <0.01). Kaplan-Meier survival analysis indicated that the median survival time was 25 months for NGF-NP astrocytoma grade I-II patients and 42 months in NGF nuclear negative (NGF-NN) astrocytoma grade I-II patients (P <0.05). In astrocytoma III-IV patients, the median survival was 7 months for NGF-NP patients and 24 months for NGF-NN patients (P <0.01). Two types of NGF with molecular weights of 13 and 36 kDa were present in astrocytoma, but only the 36 kDa NGF was found in the CSF. NGF expression elevated as the malignancy increased. Conclusions NGF-NP expression and NGF level in CSF were significant prognostic factors in astrocytoma patients. Because of the easy access of CSF, it may be developed as an index for early diagnosis and surveillance of astrocytoma.