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Development of Prognostic Indicator Based on AU-Rich Elements-Related Genes in Glioblastoma

基因 医学 肿瘤科 弗雷明翰风险评分 胶质瘤 胶质母细胞瘤 替莫唑胺 生物信息学 疾病 计算生物学 内科学 化疗 生物 遗传学 癌症研究
作者
Xiao Chen,Ying Xu,Maode Wang,Chunying Ren
出处
期刊:World Neurosurgery [Elsevier BV]
卷期号:175: e601-e613
标识
DOI:10.1016/j.wneu.2023.03.148
摘要

AREs (AU-rich elements) are important cis-acting short sequences in the 3ʹUTR (3ʹ-untranslated region) that affect messenger RNA stability and translation. However, there were no systematic researches about AREs-related genes to predict the survival of patients with GBM (glioblastoma). Differentially expressed genes were acquired from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Differentially expressed AREs-related genes were filtered by overlapping differentially expressed genes and AREs-related genes. The prognostic genes were selected to construct a risk model. Patients with GBM were categorized into 2 risk groups depending on the medium value of risk score. Gene Set Enrichment Analysis was performed to explore the potential biological pathways. We explored the correlation between the risk model and immune cells. The chemotherapy sensitivity was predicted in different risk groups. A risk model was constructed by 10 differentially expressed AREs-related genes (GNS, ANKH, PTPRN2, NELL1, PLAUR, SLC9A2, SCARA3, MAPK1, HOXB2, and EN2), and it could accurately predict the prognosis of patients with GBM. Higher risk scores for patients with GBM had a lower survival probability. The predictive power of risk model was decent. The risk score and treatment type were regarded as independent prognostic indicators. The mainly Gene Set Enrichment Analysis enrichment pathways were primary immunodeficiency and chemokine signaling pathway. Six immune cells were significant different in the 2 risk groups. There were higher abundance of macrophages M2 and neutrophils and higher sensitivity of 11 chemotherapy drugs in the high-risk group. The 10 biomarkers might be important prognostic markers and potential therapeutic targets for patients with GBM.

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