BACKGROUND Low-grade glioma (LGG)is one of the most common and aggressive neurological malignant tumors of the central nervous system. Mounting evidence indicates that aberrantly expressed long non-coding RNA (lncRNAs) and immune cell infiltration influence low-grade glioma development. Despite the increasing amount of research on lncRNA, there are very few immune-related lncRNA for LGG studies. METHODS We evaluated immune cell infiltration in 529 low-grade glioma patient specimens from TCGA and 1152 normal brain tissue samples from GTEx. ssGSEA was used to generate high, medium, and low immune cell infiltration groups and to examine the heterogeneity of the low-grade glioma immune microenvironment. A risk model of immune-related lncRNAs based on immune gene sets was developed. Sequential single-factor Cox regression, Lasso regression, and stepwise multiple Cox regression analyses uncovered immune-related lncRNAs with low-grade glioma prognostic value. Kaplan-Meier analysis, ROC analysis, and nomograms were used to predict low-grade glioma OS. At length, We performed GO term and KEGG enrichment analyses and used standardized enrichment scores (NES) to identify signaling pathways that were significantly enriched. RESULTS We identified nine immune-associated lncRNAs with low-grade glioma prognostic value (AC009283.1, AC009227.1, AL121899.1, LINC00174, LINC02166, AC018647.1, AC061961.1, NRAV, and LINC00320).These prognostic lncRNAs were used to establish prognostic markers. Kaplan-Meier Survival analysis revealed a 10-year survival rate of 22.68 % (95 % CI: 13.54-38 %] in high-risk LGG vs. 54 % (95 % CI: 39.04-74.8 %] in low-risk LGG patients. Univariate Cox regression analysis showed that the HR of risk score and 95 % CI were 1.081 and (1.060-1.102) (p < 0.001), respectively. In contrast, those from multivariate Cox regression analysis were 1.066 and (1.046-1.087) (p < 0.001). This indicated that nine LncRNAs are independent prognostic factors for patients with low-grade glioma. GSEA suggests that the identified lncRNAs influence low-grade glioma tumorigenesis and prognosis by modulating immune responses and cancer pathways. CONCLUSIONS Our data highlight the potential prognostic value of the nine immune-related lncRNA in low-grade glioma and may open new research lines and guide low-grade glioma management.

中文翻译：

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基于九种免疫相关长链非编码 RNA 的低级别胶质瘤个体化预后特征的鉴定和验证

背景低级别胶质瘤（LGG）是中枢神经系统最常见、最具侵袭性的神经系统恶性肿瘤之一。越来越多的证据表明，异常表达的长链非编码 RNA (lncRNA) 和免疫细胞浸润会影响低级别胶质瘤的发展。尽管对 lncRNA 的研究越来越多，但用于 LGG 研究的免疫相关 lncRNA 很少。方法我们评估了来自 TCGA 的 529 个低级别胶质瘤患者样本和来自 GTEx 的 1152 个正常脑组织样本中的免疫细胞浸润。ssGSEA 用于生成高、中、低免疫细胞浸润组，并检查低级别胶质瘤免疫微环境的异质性。建立了基于免疫基因集的免疫相关lncRNAs风险模型。顺序单因素 Cox 回归、Lasso 回归、逐步多元 Cox 回归分析揭示了具有低级别胶质瘤预后价值的免疫相关 lncRNA。Kaplan-Meier 分析、ROC 分析和列线图用于预测低级别胶质瘤 OS。最后，我们进行了 GO term 和 KEGG 富集分析，并使用标准化富集评分 (NES) 来识别显着富集的信号通路。结果 我们鉴定了 9 种具有低级别胶质瘤预后价值的免疫相关 lncRNA（AC009283.1、AC009227.1、AL121899.1、LINC00174、LINC02166、AC018647.1、AC061961.1和 lnc03。用于建立预后标志物。Kaplan-Meier 生存分析显示，高风险 LGG 患者的 10 年生存率为 22.68 %（95 % CI：13.54-38 %]，而低风险 LGG 患者为 54 %（95 % CI：39.04-74.8 %]） . 单变量 Cox 回归分析显示风险评分的 HR 和 95% CI 分别为 1.081 和 (1.060-1.102) (p < 0.001)。相比之下，来自多变量 Cox 回归分析的结果为 1.066 和 (1.046-1.087) (p < 0.001)。这表明 9 个 Lnc​​RNA 是低级别胶质瘤患者的独立预后因素。GSEA 表明，鉴定出的 lncRNA 通过调节免疫反应和癌症通路来影响低级别胶质瘤的发生和预后。结论 我们的数据突出了 9 种免疫相关 lncRNA 在低级别胶质瘤中的潜在预后价值，并可能开辟新的研究路线并指导低级别胶质瘤的管理。066 和 (1.046-1.087) (p < 0.001)。这表明 9 个 Lnc​​RNA 是低级别胶质瘤患者的独立预后因素。GSEA 表明，鉴定出的 lncRNA 通过调节免疫反应和癌症通路来影响低级别胶质瘤的发生和预后。结论 我们的数据突出了 9 种免疫相关 lncRNA 在低级别胶质瘤中的潜在预后价值，并可能开辟新的研究路线并指导低级别胶质瘤的管理。066 和 (1.046-1.087) (p < 0.001)。这表明 9 个 Lnc​​RNA 是低级别胶质瘤患者的独立预后因素。GSEA 表明，鉴定出的 lncRNA 通过调节免疫反应和癌症通路来影响低级别胶质瘤的发生和预后。结论 我们的数据突出了 9 种免疫相关 lncRNA 在低级别胶质瘤中的潜在预后价值，并可能开辟新的研究路线并指导低级别胶质瘤的管理。