Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road, Hefei, 230601, Anhui, P.R. China.
Anhui Medical University, No. 81, Meishan Road, Hefei, 230032, Anhui, P.R. China.
J Ovarian Res. 2022 Jan 15;15(1):8. doi: 10.1186/s13048-021-00930-w.
Long noncoding RNAs (lncRNAs) are important regulators of gene expression and can affect a variety of physiological processes. Recent studies have shown that immune-related lncRNAs play an important role in the tumour immune microenvironment and may have potential application value in the treatment and prognosis prediction of tumour patients. Epithelial ovarian cancer (EOC) is characterized by a high incidence and poor prognosis. However, there are few studies on immune-related lncRNAs in EOC. In this study, we focused on immune-related lncRNAs associated with survival in EOC.
We downloaded mRNA data for EOC patients from The Cancer Genome Atlas (TCGA) database and mRNA data for normal ovarian tissue from the Genotype-Tissue Expression (GTEx) database and identified differentially expressed genes through differential expression analysis. Immune-related lncRNAs were obtained through intersection and coexpression analysis of differential genes and immune-related genes from the Immunology Database and Analysis Portal (ImmPort). Samples in the TCGA EOC cohort were randomly divided into a training set, validation set and combination set. In the training set, Cox regression analysis and LASSO regression were performed to construct an immune-related lncRNA signature. Kaplan-Meier survival analysis, time-dependent ROC curve analysis, Cox regression analysis and principal component analysis were performed for verification in the training set, validation set and combination set. Further studies of pathways and immune cell infiltration were conducted through Gene Set Enrichment Analysis (GSEA) and the Timer data portal.
An immune-related lncRNA signature was identified in EOC, which was composed of six immune-related lncRNAs (KRT7-AS, USP30-AS1, AC011445.1, AP005205.2, DNM3OS and AC027348.1). The signature was used to divide patients into high-risk and low-risk groups. The overall survival of the high-risk group was lower than that of the low-risk group and was verified to be robust in both the validation set and the combination set. The signature was confirmed to be an independent prognostic biomarker. Principal component analysis showed the different distribution patterns of high-risk and low-risk groups. This signature may be related to immune cell infiltration (mainly macrophages) and differential expression of immune checkpoint-related molecules (PD-1, PDL1, etc.).
We identified and established a prognostic signature of immune-related lncRNAs in EOC, which will be of great value in predicting the prognosis of clinical patients and may provide a new perspective for immunological research and individualized treatment in EOC.
长链非编码 RNA(lncRNA)是基因表达的重要调控因子,可影响多种生理过程。最近的研究表明,免疫相关 lncRNA 在肿瘤免疫微环境中发挥着重要作用,可能在肿瘤患者的治疗和预后预测中具有潜在的应用价值。上皮性卵巢癌(EOC)的发病率高,预后差。然而,关于 EOC 中免疫相关 lncRNA 的研究较少。本研究重点关注与 EOC 患者生存相关的免疫相关 lncRNA。
我们从癌症基因组图谱(TCGA)数据库下载了 EOC 患者的 mRNA 数据,从基因组织表达(GTEx)数据库下载了正常卵巢组织的 mRNA 数据,并通过差异表达分析鉴定差异表达基因。通过免疫数据库和分析门户(ImmPort)中的差异基因和免疫相关基因的交集和共表达分析,获得免疫相关 lncRNA。TCGA EOC 队列中的样本被随机分为训练集、验证集和组合集。在训练集中,进行 Cox 回归分析和 LASSO 回归以构建免疫相关 lncRNA 特征。在训练集、验证集和组合集中进行 Kaplan-Meier 生存分析、时间依赖性 ROC 曲线分析、Cox 回归分析和主成分分析进行验证。通过基因集富集分析(GSEA)和 Timer 数据门户进一步研究通路和免疫细胞浸润。
鉴定出 EOC 中的免疫相关 lncRNA 特征,该特征由六个免疫相关 lncRNA(KRT7-AS、USP30-AS1、AC011445.1、AP005205.2、DNM3OS 和 AC027348.1)组成。该特征用于将患者分为高风险和低风险组。高危组的总体生存率低于低危组,在验证集和组合集中均得到了验证,该特征被确认为独立的预后生物标志物。主成分分析显示高危组和低危组的分布模式不同。该特征可能与免疫细胞浸润(主要是巨噬细胞)和免疫检查点相关分子(PD-1、PDL1 等)的差异表达有关。
我们鉴定并建立了 EOC 免疫相关 lncRNA 的预后特征,这对预测临床患者的预后具有重要价值,并且可能为 EOC 的免疫研究和个体化治疗提供新的视角。