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胶质母细胞瘤中生长停滞特异性转录物 5 和生长停滞特异性转录物 5 相关 m6A 基因特征的表征:一项观察性研究。

Characterization of growth arrest-specific transcript 5 and growth arrest-specific transcript 5-related m6A gene signature in glioma: An observational study.

机构信息

Department of Trauma Center, Zhuzhou Central Hospital, Zhuzhou, China.

Department of Trauma Intensive Care Unit, Zhuzhou Central Hospital, Zhuzhou, China.

出版信息

Medicine (Baltimore). 2024 Sep 27;103(39):e39414. doi: 10.1097/MD.0000000000039414.

Abstract

Glioma remains a significant clinical challenge and poses a dismal patient prognosis. This study focused on the long noncoding ribonucleic acid growth arrest-specific transcript 5 (GAS5) and explored the role of GAS5 and GAS5-related m6A genes in glioma. We explored the mechanisms of GAS5 expression in glioma using bioinformatic analysis based on glioma data from the Cancer Genome Atlas, GSE1142, and Chinese Glioma Genome Atlas databases. Kaplan-Meier curve analysis, nomogram construction, immune cell infiltration, drug sensitivity, mutations, and pathway analyses were performed to determine the GAS5 mechanism in glioma. Spearman correlation and weighted gene co-expression analyses were used to identify the GAS5-related m6A gene. Furthermore, we explored the correlation between GAS5, GAS5-related m6A gene, and clinical traits using analysis of variance. The Kaplan-Meier curve analysis suggested that patients with high expressions of GAS5 had better survival. The nomogram constructed indicated that GAS5 was an independent prognostic factor. Furthermore, GAS5 significantly correlated with plasma cells. GAS5 expression was significantly associated with biological processes, including oxidative phosphorylation, proteasome, and ribosome mitotic spindle. GAS5 expression was associated with sensitivity to erlotinib and gemcitabine. Differentially expressed GAS5 was significant in histology (P = 2.8e-09), grade (P = 3.7e-05), isocitrate dehydrogenase (IDH) mutation (P = 3.4e-17), 1p/19q co-deletion (Codel) status (P = 1.7e-08), and IDH mutation status and 1p/19q Codel status (P = 2.9e-18). Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) gene was significant in IDH mutation (P = .008) and IDH mutation status and 1p/19q Codel status (P = 2.1e-05). GAS5 and HNRNPC expressions reflected the malignant grade of glioma and are associated with prognosis. The abnormal expression of GAS5 could be an important biomarker for guiding erlotinib and gemcitabine use in glioma treatment. GAS5 and heterogeneous nuclear ribonucleoproteins C1/C2 are potential diagnostic and prognostic markers for glioma.

摘要

胶质母细胞瘤仍然是一个重大的临床挑战,患者预后较差。本研究聚焦于长链非编码 RNA 生长停滞特异性转录物 5(GAS5),并探讨了 GAS5 和 GAS5 相关 m6A 基因在胶质母细胞瘤中的作用。我们使用基于癌症基因组图谱、GSE1142 和中国脑胶质瘤基因组图谱数据库的胶质母细胞瘤数据进行了生物信息学分析,探讨了 GAS5 在胶质母细胞瘤中的表达机制。通过 Kaplan-Meier 曲线分析、列线图构建、免疫细胞浸润、药物敏感性、突变和通路分析,确定了 GAS5 在胶质母细胞瘤中的机制。Spearman 相关性和加权基因共表达分析用于鉴定 GAS5 相关的 m6A 基因。此外,我们还使用方差分析探讨了 GAS5、GAS5 相关 m6A 基因与临床特征的相关性。Kaplan-Meier 曲线分析表明,GAS5 高表达的患者生存更好。构建的列线图表明 GAS5 是一个独立的预后因素。此外,GAS5 与浆细胞显著相关。GAS5 的表达与包括氧化磷酸化、蛋白酶体和核糖体有丝分裂纺锤体在内的生物学过程显著相关。GAS5 的表达与厄洛替尼和吉西他滨的敏感性相关。组织学(P = 2.8e-09)、分级(P = 3.7e-05)、异柠檬酸脱氢酶(IDH)突变(P = 3.4e-17)、1p/19q 共缺失(Codel)状态(P = 1.7e-08)和 IDH 突变状态和 1p/19q Codel 状态(P = 2.9e-18)差异表达的 GAS5 显著。异质性核核糖核蛋白 C1/C2(HNRNPC)基因在 IDH 突变(P =.008)和 IDH 突变状态和 1p/19q Codel 状态(P = 2.1e-05)中显著。GAS5 和 HNRNPC 的表达反映了胶质母细胞瘤的恶性程度,并与预后相关。GAS5 的异常表达可能是指导胶质母细胞瘤治疗中厄洛替尼和吉西他滨使用的重要生物标志物。GAS5 和异质性核核糖核蛋白 C1/C2 是胶质母细胞瘤潜在的诊断和预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767c/11441912/44f8e35883f4/medi-103-e39414-g001.jpg

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