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.
Highlights
Gliomas represent the most common primary brain and central nervous system tumors worldwide and occur almost exclusively in the following four lobes of the brain: frontal (23.6%), temporal (17.4%), parietal (10.6%), and occipital (2.8%), leading to significant morbidity and mortality in adults, especially elderly people [1, 2]
It was revealed that the expression levels of Notch 1, Notch 2, and Notch 3 were associated with the clinical stage of glioma (P < 0:05, Table 1), suggesting that high expression of Notch proteins may contribute to the progression of glioma
Analyzing the related biological macromolecules of the onset and clinical stage of glioma and exploring the relationship between it and the prognosis of patients are of great value to clinical diagnosis and treatment, as well as the improvement of the prognosis of patients
Summary
Gliomas represent the most common primary brain and central nervous system tumors worldwide and occur almost exclusively in the following four lobes of the brain: frontal (23.6%), temporal (17.4%), parietal (10.6%), and occipital (2.8%), leading to significant morbidity and mortality in adults, especially elderly people [1, 2]. Elderly patients already account for 10-25% of all 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 ranging only from 4 to 6 months [3]. In this context, the increasing aging of the population will contribute to at least twofold increase in the number of glioma diagnoses in elderly patients in the following two decades [4, 5]. Survivin is known as a member of the inhibitor of apoptosis family and is nearly undetectable in most normal tissues in adults It is highly expressed in almost all human malignancies [9]. 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
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