鉴定卵巢癌中失调免疫 lncRNA 的两种分子亚型。
Identification of two molecular subtypes of dysregulated immune lncRNAs in ovarian cancer.
机构信息
Department of Gynaecology and Obstetrics, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
出版信息
Exp Biol Med (Maywood). 2021 Mar;246(5):547-559. doi: 10.1177/1535370220972024. Epub 2020 Nov 17.
Long non-coding RNA (lncRNA) has increasingly been identified as a key regulator in pathologies such as cancer. Multiple platforms were used for comprehensive analysis of ovarian cancer to identify molecular subgroups. However, lncRNA and its role in mapping the ovarian cancer subpopulation are still largely unknown. RNA-sequencing and clinical characteristics of ovarian cancer were acquired from The Cancer Genome Atlas database (TCGA). A total of 52 lncRNAs were identified as aberrant immune lncRNAs specific to ovarian cancer. We redefined two different molecular subtypes, C1(188) and C2(184 samples), in "iClusterPlus" R package, among which C2 grouped ovarian cancer samples have higher survival probability and longer median survival time ( <0.05) with activated IFN-gamma response, Wound Healing and Cytotoxic lymphocytes signal; 456 differentially expressed genes were acquired in C1 and C2 subtypes using limma (3.40.6) package, among which 419 were up-regulated and 37 were down-regulated, in TCGA dataset. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis revealed that these genes were actively involved in ECM-receptor interaction, PI3K-Akt signaling pathway interaction KEGG pathway. Compared with the existing immune subtype, the Cluster2 sample showed a substantial increase in the proportion of the existing C2 immune subtype, accounting for 81.37%, which was associated with good prognosis. Our C1 subtype contains only 56.49% of the existing immune C1 and C4, which also explains the poor prognosis of C1. Furthermore, 52 immune-related lncRNAs were used to divide the TCGA-endometrial cancer and cervical cancer samples into two categories, and C2 had a good prognosis. The differentially expressed genes were highly correlated with immune-cell-related pathways. Based on lncRNA, two molecular subtypes of ovarian cancer were identified and had significant prognostic differences and immunological characteristics.
长链非编码 RNA（lncRNA）已被越来越多地鉴定为癌症等病理学中的关键调节因子。多个平台被用于全面分析卵巢癌，以确定分子亚群。然而，lncRNA 及其在绘制卵巢癌亚群中的作用在很大程度上仍然未知。从癌症基因组图谱数据库（TCGA）获得了 RNA 测序和卵巢癌的临床特征。总共鉴定出 52 个异常免疫 lncRNA，这些 lncRNA 是卵巢癌特有的。我们在“iClusterPlus”R 包中重新定义了两种不同的分子亚型 C1（188 个样本）和 C2（184 个样本），其中 C2 分组的卵巢癌样本具有更高的生存概率和更长的中位生存时间（<0.05），并激活 IFN-γ 反应、伤口愈合和细胞毒性淋巴细胞信号；使用 limma（3.40.6）包在 C1 和 C2 亚型中获得了 456 个差异表达基因，其中 419 个上调，37 个下调，在 TCGA 数据集。基因本体论和京都基因与基因组百科全书（KEGG）功能富集分析表明，这些基因积极参与细胞外基质受体相互作用、PI3K-Akt 信号通路相互作用 KEGG 通路。与现有的免疫亚型相比，Cluster2 样本中现有的 C2 免疫亚型比例显著增加，占 81.37%，与良好的预后相关。我们的 C1 亚型仅包含 56.49%的现有免疫 C1 和 C4，这也解释了 C1 的不良预后。此外，使用 52 个免疫相关 lncRNA 将 TCGA 子宫内膜癌和宫颈癌样本分为两类，C2 具有良好的预后。差异表达基因与免疫细胞相关途径高度相关。基于 lncRNA，鉴定出两种卵巢癌分子亚型，具有显著的预后差异和免疫特征。
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