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一种与铜死亡相关的基因DLAT作为一种新的预后标志物及其与低级别胶质瘤免疫浸润的相关性

A cuproptosis-related gene DLAT as a novel prognostic marker and its relevance to immune infiltration in low-grade gliomas.

作者信息

Gao Peng, Li Huaixu, Qiao Yang, Nie Jianyu, Cheng Sheng, Tang Guozhang, Dai Xingliang, Cheng Hongwei

机构信息

Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, PR China.

Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, PR China.

出版信息

Heliyon. 2024 Jun 6;10(11):e32270. doi: 10.1016/j.heliyon.2024.e32270. eCollection 2024 Jun 15.

Abstract

DLAT has been recognized as a cuproptosis-related gene that is crucial for cuproptosis in earlier research. The study is to look at how DLAT affects individuals with low-grade glioma's prognosis and immune infiltration. The Genotype-Tissue Expression (GTEx) database and the TCGA database were used in this work to download RNAseq data in TPM format. DLAT was found to be overexpressed in LGG by comparing DLAT expression levels between LGG and normal brain tissue, and the expression of DLAT was verified by immunohistochemistry and semi-quantitative analysis. Then, the functional enrichment analysis revealed that the biological functional pathways and possible signal transduction pathways involved were primarily focused on extracellular matrix organization, transmembrane transporter complex, ion channel complex, channel activity, neuroactive ligand-receptor interaction, complement and coagulation cascades, and channel activity. The level of immune cell infiltration by plasmacytoid dendritic cells and CD8 T cells was subsequently evaluated using single-sample gene set enrichment analysis, which showed that high DLAT expression was inversely connected with that level of infiltration. The link between the methylation and mRNA transcription of DLAT was then further investigated via the MethSurv database, and the results showed that DLAT's hypomethylation status was linked to a poor outcome. Finally, by evaluating the prognostic value of DLAT using the Cox regression analysis and Kaplan-Meier technique, a column line graph was created to forecast the overall survival (OS) rate at 1, 3, and 5 years after LGG identification. The aforementioned results demonstrated that high DLAT expression significantly decreased OS and DSS, and that overexpression of DLAT in LGG was significantly linked with WHO grade, IDH status, primary therapy outcome, overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) events. DLAT was discovered as a separate predictive sign of OS in the end. DLAT might thus represent a brand-new predictive biomarker.

摘要

在早期研究中,DLAT已被确认为一种与铜死亡相关的基因,对铜死亡至关重要。本研究旨在探讨DLAT如何影响低级别胶质瘤患者的预后和免疫浸润。在这项工作中,使用基因型-组织表达(GTEx)数据库和TCGA数据库下载TPM格式的RNAseq数据。通过比较低级别胶质瘤(LGG)与正常脑组织中DLAT的表达水平,发现DLAT在LGG中过表达,并通过免疫组织化学和半定量分析验证了DLAT的表达。然后,功能富集分析表明,所涉及的生物学功能途径和可能的信号转导途径主要集中在细胞外基质组织、跨膜转运体复合物、离子通道复合物、通道活性、神经活性配体-受体相互作用、补体和凝血级联反应以及通道活性。随后,使用单样本基因集富集分析评估浆细胞样树突状细胞和CD8 T细胞的免疫细胞浸润水平,结果表明DLAT高表达与浸润水平呈负相关。然后通过MethSurv数据库进一步研究DLAT的甲基化与mRNA转录之间的关系,结果表明DLAT的低甲基化状态与不良预后相关。最后,通过使用Cox回归分析和Kaplan-Meier技术评估DLAT的预后价值,创建了一个柱状线图来预测LGG确诊后1、3和5年的总生存率(OS)。上述结果表明,DLAT高表达显著降低了OS和疾病特异性生存率(DSS),并且LGG中DLAT的过表达与世界卫生组织(WHO)分级、异柠檬酸脱氢酶(IDH)状态、初始治疗结果、总生存率(OS)、疾病特异性生存率(DSS)和无进展生存期(PFI)事件显著相关。最终,DLAT被发现是OS的一个独立预测指标。因此,DLAT可能代表一种全新的预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/245f/11219321/70deb2add1cf/gr1.jpg

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