RESUMO
The median survival time of lower grade glioma (LGG) tumors spans a wide range of 2-10 years and is highly dependent on the molecular characteristics and tumor location. Currently, there is no prognostic predictor for these tumors based on autophagy-related (ATG) genes. A prognostic risk score model based on the most significant seven ATG genes was established for LGG. These seven genes, including GRID2, FOXO1, MYC, PTK6, IKBKE, BIRC5, and TP73, have been screened as potentially therapeutic targets. The Kaplan-Meier survival curve analyses validated that patients with high or low risk scores had significantly different overall survival. Following the multivariate Cox regression and area under the ROC curve (AUC) analysis, a final prognostic model based on age, World Health Organization grade, 1p19q-codeletion status, and ATG risk score was performed as an independent prognostic indicator (training set: p = 4.09E-05, AUC = 0.901; validation set-1: p = .00069, AUC = 0.808; validation set-2: p = .0376, AUC = 0.830). Subsequently, a prognostic nomogram was constructed for individualized survival prediction. The calibration plots showed excellent predict efficiency between probability and actual overall survival. In this study, we provided several potential biomarkers for further developing potentially therapeutic targets of LGG. We also established a prognostic model and nomogram to improve the clinical glioma management and assist individualized survival prediction.
Assuntos
Autofagia/fisiologia , Neoplasias Encefálicas/patologia , Glioma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Feminino , Glioma/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Fatores de RiscoRESUMO
Although pituitary tumors are among the most common types of brain tumor, the underlying molecular mechanism of this disease remains obscure. To this end, the role of sirtuin 1 (SIRT1) in pituitary tumors was reported. The results of reverse transcriptionquantitative PCR and immunohistochemistry revealed that sirtuin 1 (SIRT1) expression was downregulated in the tumor tissues of patients with pituitary tumors. In vitro experiments of the present study demonstrated that SIRT1 upregulation suppressed pituitary tumor cell line growth, while SIRT1 downregulation demonstrated the opposite effect. Additionally, it was determined that the enzymatic activity of SIRT1 was required for its cellular function. A mechanistic experiment determined that SIRT1 negatively regulated pituitary tumortransforming gene 1 (PTTG1) expression through the deacetylation of histone (H)3 lysine (K)9ac at the promoter region of PTTG1. Moreover, H3K9ac levels at the PTTG1 promoter were determined to be an essential regulatory element for PTTG1 expression. Thus, it was concluded that the SIRT1/H3K9ac/PTTG1 axis contributed to pituitary tumor formation and may represent a potential therapeutic strategy.
Assuntos
Neoplasias Hipofisárias , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Securina/genética , Sirtuína 1/genética , Sirtuína 1/metabolismoRESUMO
Glioblastoma (GBM) is the most aggressive malignant brain tumour, with high morbidity and mortality rates. Currently, there is a lack of systematic and comprehensive analysis on the prognostic significance of alternative splicing (AS) profiling for GBM. The GBM data, including RNA-sequencing, corresponding clinical information and the expression levels of splicing factor genes, were downloaded from The Cancer Genome Atlas and the SpliceAid2 database. The prognostic models were assessed by the least absolute shrinkage and selection operator Cox regression analysis. The correlation network between survival-associated AS events and splicing factors was plotted. Prognostic models were built for every AS event type and performed well for risk stratification in patients with GBM. The final prognostic signature served as an independent prognostic factor [hazard ratio (HR), 4.61; 95% confidence interval (CI), 2.97-7.16; P=9.66×10-12] for several clinical parameters, including age, sex, isocitrate dehydrogenase mutation, O6-methylguanine-DNA methyltransferase promoter methylation and risk score. The HR for risk score with GBM was 1.0063 (95% CI, 1.0024-1.0103). The splicing regulatory network indicated that heat shock protein b-1, protein arginine N-methyltransferase 5, protein FAM50B and endoplasmic reticulum chaperone BiP genes were independent prognostic factors for GBM. The results of the present study support the ongoing effort in developing novel genomic models and providing potentially more effective treatment options for patients with GBM.
RESUMO
OBJECTIVE: To discuss the operation method and characteristic of correcting upper eyelid depression by transposition of orbital septum fat. METHODS: During the double eyelid surgery, we set.the lateral orbital septum fat completely free, while the bottom is still connected with the middle orbital septum fat. We separate a tunnel from the middle to the inner side in orbital septum, and the separated orbital septum fat is transposed to the inner side of orbital septum by the tunnel with suturing fixation. RESULTS: From March 2008 to October 2013, 51 cases with upper eyelid depression were treated successfully. Patients were followed up for 3 months to 3 years (average, 7. 5 months) with sustained aesthetic results. CONCLUSIONS: Orbital septum fat transposition can successfully correct the upper eyelid depression. It should become a regular procedure in blepharoplasty.