Development of an m6A-Related lncRNAs Signature Predicts Tumor Stemness and Prognosis for Low-Grade Glioma Patients

IF 3.8 3区 医学 Q2 CELL & TISSUE ENGINEERING
Dahua Xu, Peihu Li, Chunrui Zhang, Yutong Shen, Jiale Cai, Qingchen Wei, Meng Cao, Zhizhou Xu, Deng Wu, Hong Wang, Xiaoman Bi, Bo Wang, Kongning Li
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引用次数: 0

Abstract

Background. Growing evidence has revealed that m6A modification of long noncoding RNAs (lncRNAs) dynamically controls tumor stemness and tumorigenesis-related processes. However, the prognostic significance of m6A-related lncRNAs and their associations with stemness in low-grade glioma (LGG) remain to be clarified. Methods. A multicenter transcriptome analysis of lncRNA expression in 1,247 LGG samples was performed in this study. The stemness landscape of LGG tumors was presented and associations with clinical features were revealed. The m6A-related lncRNAs were identified between stemness groups and were further prioritized via least absolute shrinkage and selection operator Cox regression analysis. A risk score model based on m6A-related lncRNAs was constructed and validated in external LGG datasets. Results. Based on the expression of LINC02984, PFKP-DT, and CRNDE, a risk model and nomogram were constructed; they successfully predicted the survival of patients and were extended to external datasets. Significant correlations were observed between the risk score and tumor stemness. Moreover, patients in different risk groups exhibited distinct tumor immune microenvironments and immune signatures. We finally provided several potential compounds suitable for specific risk groups, which may aid in LGG treatment. Conclusions. This novel signature presents noteworthy value in the prediction of prognosis and stemness status for LGG patients and will foster future research on the development of clinical regimens.
开发与 m6A 相关的 lncRNAs Signature 预测低级别胶质瘤患者的肿瘤干性和预后
背景。越来越多的证据表明,长非编码RNA(lncRNA)的m6A修饰可动态控制肿瘤干性和肿瘤发生相关过程。然而,m6A相关lncRNA的预后意义及其与低级别胶质瘤(LGG)干性的关联仍有待明确。研究方法本研究对1 247份LGG样本中的lncRNA表达进行了多中心转录组分析。结果显示了LGG肿瘤的干性结构,并揭示了其与临床特征的关联。干性组之间的m6A相关lncRNA被识别出来,并通过最小绝对缩减和选择算子Cox回归分析进一步确定了它们的优先级。构建了基于m6A相关lncRNA的风险评分模型,并在外部LGG数据集中进行了验证。结果根据LINC02984、PFKP-DT和CRNDE的表达,构建了风险模型和提名图;它们成功地预测了患者的生存率,并扩展到了外部数据集。在风险评分和肿瘤干性之间观察到了显著的相关性。此外,不同风险组的患者表现出不同的肿瘤免疫微环境和免疫特征。最后,我们提供了几种适合特定风险组的潜在化合物,它们可能有助于 LGG 的治疗。结论这种新型特征在预测LGG患者的预后和干细胞状态方面具有显著价值,并将促进未来临床治疗方案的开发研究。
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来源期刊
Stem Cells International
Stem Cells International CELL & TISSUE ENGINEERING-
CiteScore
8.10
自引率
2.30%
发文量
188
审稿时长
18 weeks
期刊介绍: Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials. Topics covered include, but are not limited to: embryonic stem cells; induced pluripotent stem cells; tissue-specific stem cells; stem cell differentiation; genetics and epigenetics; cancer stem cells; stem cell technologies; ethical, legal, and social issues.
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