Objective To investigate the expression pattern and clinical significance of spermidine/ spermine N1-acetyltransferase 1( SAT1), ferroptosis regulatory genen, in brain gliomas. Methods The clinical data and expression profile of glioma tissue samples in a total of 3 batches of 1 720 patients were obtained from CGGA and TCGA database. There were 325, 693 and 702 cases in CGGA-325 group, CGGA- 693 group and TCGA group, respectively. The expression trend of SAT1 gene and its correlation with pathology,molecular pathology and prognosis were analyzed. Vitro assays was used to study the biological function of SAT1 gene in glioma. Kaplan-Meier survival curve was used to compare the survival differences of glioma patients with different SAT1 gene expression. Receiver operating characteristic( ROC) curve was used to evaluate the predictive effect of SAT1 on 1-year and 3-year overall survival of patients with glioma. Results In glioma tissue samples, SAT1 showed highest expression in IDH wildtype glioblastomas and lowest expression in IDH mutant and 1p19q codeleted lower grade gliomas( P<0.001 in all 3 groups). In WHO grade Ⅲ and Ⅳ giomas, patients with high expression of SAT1 showed more unfavorable prognosis( the median survival time of patients with high and low SAT1 expression in different databases and grades was as below: CGGA-325 group, WHO grade Ⅲ patients, 485 days and 1 321 days, P< 0.05; CGGA-325 group, WHO grade Ⅳ patients, 286 days and 493 days, P < 0.05; CGGA-693 group, WHO grade Ⅲ patients, 836 days and 2982 days, P < 0.05; CGGA-693 group, WHO grade Ⅳ patients, 356 days and 459 days, P< 0.05; TCGA group, WHO grade Ⅲ patients, 31.57 months and 114 months, P< 0.05; TCGA group, WHO grade Ⅳ patients, 11.24 months and 13.77 months, P< 0.05). The area under the curve( AUC) of SAT1 on 1-year and 3-year overall survival in CGGA-325 group was 0.725 and 0.793, respectively, 0.615 and 0.671 in CGGA-693 group, 0.791 and 0.808 in TCGA group,( P<0.001). In vitro assays showed that down-regulation of SAT1 in glioma cells could inhibit cell proliferation( P<0.05 after 24 hours and 48 hours of the treatment). Conclusions SAT1 was associated with glioma grade, molecular subtypes and patients' prognosis, which might due to the proliferation promotion effects.
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张传宝 刘汉杰 王志亮 王政 王洪军.铁死亡调控基因亚精胺/精胺N1-乙酰基转移酶1在脑胶质瘤中的 表达及临床意义[J].神经疾病与精神卫生,2021,21(5): DOI :10.3969/j. issn.1009-6574.2021.05.005.