N6-甲基腺苷相关长链非编码RNA作为子宫内膜癌潜在的预后生物标志物
N6-Methyladenosine-Related Long Noncoding RNAs as Potential Prognosis Biomarkers for Endometrial Cancer.
作者信息
Shi Rui, Wang Ziwei, Zhang Jun, Yu Zhicheng, An Lanfen, Wei Sitian, Feng Dilu, Wang Hongbo
机构信息
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People's Republic of China.
出版信息
Int J Gen Med. 2021 Nov 16;14:8249-8262. doi: 10.2147/IJGM.S336403. eCollection 2021.
PURPOSE
Endometrial cancer (EC) is a common gynaecologic malignancy with an increasing incidence rate and mortality in recent years. N6-methylandenosine (m6A)-related long noncoding RNA (lncRNA) plays a vital role in EC, emerging as one of the most abundant RNA modifications.
MATERIALS AND METHODS
The Cancer Genome Atlas (TCGA) database and UCSC Xena were used to download data related to EC. Survival and univariate and multifactorial prognostic analyses were performed for m6A-related lncRNAs. The expression levels of the three lncRNAs were verified using q-PCR. A nomogram was used to create a clinical tool to assess overall survival. To investigate the relationship between m6A-related lncRNA and EC, we downloaded differential genes related to EC from the TCGA database and mined three m6A-related lncRNAs, namely SCARNA9, TRAF3IP2-AS1, and AL133243.2. The data were categorized into high- and low-risk groups based on m6A-associated lncRNA.
RESULTS
Survival analysis revealed that the high-risk group had a lower survival rate. Survival analysis of three m6A-associated lncRNAs revealed that cases with high expression of SCARNA9 tended to have a poorer prognosis, whereas the opposite was true for TRAF3IP2-AS1, AL133243.2. Univariate and multifactorial prognostic analyses suggested statistical differences in patients' age, FIGO stage, pathological grade, risk score, and prognosis of EC, which was confirmed by results of the separate prognostic factor analysis for the three lncRNAs. Risk status was validated as an independent prognostic indicator, and the prognostic nomogram combined patient age, pathological stage, and FIGO classification to assess 3-5-year survival. Cases from high- and low-risk groups were analysed for the tumour microenvironment and immune cell scores, and stromal cell scores were found to be lower in the high-risk group. Correlations were analysed using different databases for immune cell classification.
CONCLUSION
m6A-related lncRNAs may play a key role in the diagnosis and treatment of EC as targets of prognosis and the immune microenvironment.
目的
子宫内膜癌（EC）是一种常见的妇科恶性肿瘤，近年来其发病率和死亡率呈上升趋势。N6-甲基腺苷（m6A）相关的长链非编码RNA（lncRNA）在EC中起着至关重要的作用，它是最丰富的RNA修饰之一。
材料与方法
利用癌症基因组图谱（TCGA）数据库和加州大学圣克鲁兹分校的Xena数据库下载与EC相关的数据。对m6A相关lncRNAs进行生存分析以及单因素和多因素预后分析。使用q-PCR验证三种lncRNAs的表达水平。使用列线图创建一种临床工具来评估总生存期。为了研究m6A相关lncRNA与EC之间的关系，我们从TCGA数据库下载了与EC相关的差异基因，并挖掘出三种m6A相关lncRNAs，即SCARNA9、TRAF3IP2-AS1和AL133243.2。根据m6A相关lncRNA将数据分为高风险组和低风险组。
结果
生存分析显示高风险组的生存率较低。对三种m6A相关lncRNAs的生存分析表明，SCARNA9高表达的病例往往预后较差，而TRAF3IP2-AS1、AL133243.2则相反。单因素和多因素预后分析表明，患者的年龄、国际妇产科联盟（FIGO）分期、病理分级、风险评分和EC预后存在统计学差异，这一点在对三种lncRNAs的单独预后因素分析结果中得到了证实。风险状态被验证为独立的预后指标，预后列线图结合患者年龄、病理分期和FIGO分类来评估3至5年生存率。对高风险组和低风险组的病例进行肿瘤微环境和免疫细胞评分分析，发现高风险组的基质细胞评分较低。使用不同数据库对免疫细胞分类进行相关性分析。
结论
m6A相关lncRNAs可能作为预后和免疫微环境的靶点在EC的诊断和治疗中发挥关键作用。
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