High Expressions of Notch and Survivin in Elderly Patients with Glioma Contribute to an Unfavorable Prognosis

Abstract

Gliomas account for 24% of all primary brain and central nervous system tumors. To date, elderly patients constitute 10-25% of patients with a diagnosis of glioblastoma multiforme, but limited attention has been put on their optimal treatment, largely due to a very poor expected survival (only 4-6 months). Unraveling the molecular mechanism of gliomas provides an opportunity to develop novel biomarkers and therapeutic targets. In this study, we collected fasting blood samples from elderly patients diagnosed with glioma and who received treatment in our hospital between May 2016 and May 2019 and determined the expression levels of Notch and Survivin proteins in different clinical stages and their relationship with patient survival. A total of 68 healthy volunteers in this hospital during the same period served as healthy controls. Compared with the healthy controls, the expressions of Notch 1, Notch 2, Notch 3, and Survivin protein in the serum of elderly glioma patients were remarkably increased ( $P<0.05$ ), but the expression of caspase-3 protein declined ( $P<0.05$ ). As the clinical stage of the patient advanced, the expressions of Notch 1, Notch 2, Notch 3, and Survivin increased, and this increase was statistically significant ( $P<0.05$ ). It was observed that high expressions of serum Notch 1, Notch 2, Notch 3, and Survivin were associated with poor overall survival of elderly patients with glioma. We used γ-secretase inhibitor MRK-003 and specific ligand Jagged1 to alter the Notch pathway in U251 cells. It was revealed that MRK-003 incubation effectively suppressed the mRNA expression of Survivin in U251 cells, but Jagged1 stimulation significantly promoted the mRNA expression of Survivin in U251 cells. Results of MTT and transwell migration assays revealed reduced U251 cell viability and migration following MRK-003 treatment and enhanced cell viability and migration following Jagged1 stimulation. In conclusion, the finding obtained from these results supports that Notch and Survivin proteins contribute to the development of glioma in elderly patients and could serve as prognostic factors.