Maimaiti Aierpati, Jiang Lei, Wang Xixian, Shi Xin, Pei Yinan, Hao Yujun, Paerhati Halimureti, Zibibula Yierpan, Abudujielili Abulikemu, Kasimu Maimaitijiang
Department of Functional Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
Department of Functional Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
Clin Neurol Neurosurg. 2021 Feb;201:106464. doi: 10.1016/j.clineuro.2020.106464. Epub 2021 Jan 5.
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.
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.
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.
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.
低级别胶质瘤（LGG）是中枢神经系统最常见且侵袭性强的神经恶性肿瘤之一。越来越多的证据表明，异常表达的长链非编码RNA（lncRNAs）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，但针对LGG研究的免疫相关lncRNA却很少。
我们评估了来自TCGA的529例低级别胶质瘤患者标本和来自GTEx的1152例正常脑组织样本中的免疫细胞浸润情况。采用单样本基因集富集分析（ssGSEA）生成高、中、低免疫细胞浸润组，并检测低级别胶质瘤免疫微环境的异质性。基于免疫基因集构建了免疫相关lncRNAs的风险模型。通过序贯单因素Cox回归、Lasso回归和逐步多元Cox回归分析，发现具有低级别胶质瘤预后价值的免疫相关lncRNAs。采用Kaplan-Meier分析、ROC分析和列线图预测低级别胶质瘤的总生存期（OS）。最后，我们进行了基因本体（GO）术语和京都基因与基因组百科全书（KEGG）富集分析，并使用标准化富集分数（NES）来识别显著富集的信号通路。
我们鉴定出9个具有低级别胶质瘤预后价值的免疫相关lncRNAs（AC009283.1、AC009227.1、AL121899.1、LINC00174、LINC02166、AC018647.1、AC061961.1、NRAV和LINC00320）。这些预后lncRNAs被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%）。单因素Cox回归分析显示，风险评分的HR及95%CI分别为1.081和（1.060-1.102）（p<0.001）。相比之下，多因素Cox回归分析的结果为1.066和（1.046-1.087）（p<0.001）。这表明这9个lncRNAs是低级别胶质瘤患者的独立预后因素。基因集富集分析（GSEA）表明，所鉴定的lncRNAs通过调节免疫反应和癌症通路影响低级别胶质瘤的肿瘤发生和预后。
我们的数据突出了这9个免疫相关lncRNA在低级别胶质瘤中的潜在预后价值，可能开辟新的研究方向并指导低级别胶质瘤的管理。
