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Identification of two molecular subtypes of dysregulated immune lncRNAs in ovarian cancer
Experimental Biology and Medicine ( IF 3.2 ) Pub Date : 2020-11-17 , DOI: 10.1177/1535370220972024
Xiaojun Liu 1 , Jinghai Gao 1 , Jing Wang 1 , Jing Chu 1 , Jiahao You 1 , Zhijun Jin 1
Affiliation  

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 (P <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.



中文翻译:

鉴定卵巢癌中两种失调的免疫 lncRNA 分子亚型

长链非编码 RNA (lncRNA) 越来越多地被认为是癌症等疾病的关键调节因子。使用多个平台对卵巢癌进行综合分析,以确定分子亚群。然而,lncRNA 及其在定位卵巢癌亚群中的作用仍然很大程度上未知。从癌症基因组图谱数据库(TCGA)获得卵巢癌的 RNA 测序和临床特征。共有 52 个 lncRNA 被鉴定为卵巢癌特异性异常免疫 lncRNA。我们在“iClusterPlus”R包中重新定义了两种不同的分子亚型C1(188)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(P<0.05) 具有激活的 IFN-γ 反应、伤口愈合和细胞毒性淋巴细胞信号;在TCGA数据集中,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,其中上调419个,下调37个。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,这些基因积极参与了ECM-受体相互作用、PI3K-Akt信号通路相互作用的KEGG通路。与现有免疫亚型相比,Cluster2样本显示现有C2免疫亚型的比例大幅增加,占81.37%,与预后良好相关。我们的C1亚型只包含现有免疫C1和C4的56.49%,这也解释了C1预后不良的原因。此外,52个免疫相关lncRNA用于将TCGA-子宫内膜癌和宫颈癌样本分为两类,C2预后良好。差异表达的基因与免疫细胞相关通路高度相关。基于 lncRNA,鉴定了两种卵巢癌分子亚型,并具有显着的预后差异和免疫学特征。

更新日期:2020-11-18
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