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基于3个长链非编码RNA特征预测子宫内膜癌的临床结局

Prediction of Clinical Outcome in Endometrial Carcinoma Based on a 3-lncRNA Signature.

作者信息

Ding Hongmei, Jiang Fei, Deng Lifeng, Wang Juan, Wang Ping, Ji Mintao, Li Jie, Shi Weiqiang, Pei Yufang, Li Jiafu, Zhang Yue, Zhang Zengli, Chen Youguo, Li Bingyan

机构信息

Deparment of Nutrition and Food Hygiene, Medical College of Soochow University, Suzhou, China.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Front Cell Dev Biol. 2022 Feb 1;9:814456. doi: 10.3389/fcell.2021.814456. eCollection 2021.

Abstract

Endometrial carcinoma (EC) is one of the common gynecological cancers with increasing incidence and revived mortality recently. Given the heterogeneity of tumors and the complexity of lncRNAs, a panel of lncRNA biomarkers might be more precise and stable for prognosis. In the present study, we developed a new lncRNA model to predict the prognosis of patients with EC. EC-associated differentially expressed long noncoding RNAs (lncRNAs) were identified from The Cancer Genome Atlas (TCGA). Univariate COX regression and least absolute shrinkage and selection operator (LASSO) model were selected to find the 8-independent prognostic lncRNAs of EC patient. Furthermore, the risk score of the 3-lncRNA signature for overall survival (OS) was identified as CTD-2377D24.6 expression × 0.206 + RP4-616B8.5 × 0.341 + RP11-389G6.3 × 0.343 by multivariate Cox regression analysis. According to the median cutoff value of this prognostic signature, the EC samples were divided into two groups, high-risk set (3-lncRNAs at high levels) and low-risk set (3-lncRNAs at low levels), and the Kaplan-Meier survival curves demonstrated that the low-risk set had a higher survival rate than the high-risk set. In addition, the 3-lncRNA signature was closely linked with histological subtype ( = 0.0001), advanced clinical stage ( = 0.011), and clinical grade ( < 0.0001) in EC patients. Our clinical samples also confirmed that RP4-616B8.5, RP11-389G6.3, and CTD-2377D24.6 levels were increased in tumor tissues by qRT-PCR and hybridization. Intriguingly, the -value of combined 3-lncRNAs was lower than that of each lncRNA, indicating that the 3-lncRNA signature also showed higher performance in EC tissue than paracancerous. Functional analysis revealed that cortactin might be involved in the mechanism of 3-lncRNA signatures. These findings provide the first hint that a panel of lncRNAs may play a critical role in the initiation and metastasis of EC, indicating a new signature for early diagnosis and therapeutic strategy of uterine corpus endometrial carcinoma.

摘要

子宫内膜癌(EC)是常见的妇科癌症之一,近年来其发病率呈上升趋势,死亡率也有所回升。鉴于肿瘤的异质性和长链非编码RNA(lncRNA)的复杂性,一组lncRNA生物标志物可能对预后的预测更为精确和稳定。在本研究中,我们开发了一种新的lncRNA模型来预测EC患者的预后。从癌症基因组图谱(TCGA)中鉴定出与EC相关的差异表达长链非编码RNA(lncRNA)。采用单因素COX回归和最小绝对收缩和选择算子(LASSO)模型来寻找EC患者的8个独立预后lncRNA。此外,通过多因素Cox回归分析确定3-lncRNA特征对总生存期(OS)的风险评分为CTD-2377D24.6表达量×0.206 + RP4-616B8.5×0.341 + RP11-389G6.3×0.343。根据该预后特征的中位数临界值,将EC样本分为两组,高风险组(3种lncRNA水平高)和低风险组(3种lncRNA水平低),Kaplan-Meier生存曲线表明低风险组的生存率高于高风险组。此外,在EC患者中,3-lncRNA特征与组织学亚型(P = 0.0001)、临床晚期(P = 0.011)和临床分级(P < 0.0001)密切相关。我们的临床样本也通过qRT-PCR和杂交证实肿瘤组织中RP4-616B8.5、RP11-389G6.3和CTD-2377D24.6的水平升高。有趣的是,联合3种lncRNA的P值低于每种lncRNA,表明3-lncRNA特征在EC组织中也比癌旁组织表现出更高的性能。功能分析显示,皮层肌动蛋白可能参与了3-lncRNA特征的机制。这些发现首次提示一组lncRNA可能在EC的发生和转移中起关键作用,为子宫体子宫内膜癌的早期诊断和治疗策略指明了一种新的特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186f/8844015/ee18c1d2e3c9/fcell-09-814456-g001.jpg

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