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Identification and Validation of EMT-Related lncRNA Prognostic Signature for Colorectal Cancer
Frontiers in Genetics ( IF 3.7 ) Pub Date : 2021-09-22 , DOI: 10.3389/fgene.2021.723802
Danfeng Li 1 , Xiaosheng Lin 1 , Binlie Chen 1, 2 , Zhiyan Ma 1, 2 , Yongming Zeng 1 , Huaiming Wang 1
Affiliation  

Background: This study aimed to explore the biological functions and prognostic role of Epithelial-mesenchymal transition (Epithelial-mesenchymal transition)-related lncRNAs in colorectal cancer (CRC).

Methods: The Cancer Genome Atlas database was applied to retrieve gene expression data and clinical information. An EMT-related lncRNA risk signature was constructed relying on univariate Cox regression, Least Absolute Shrinkage and Selector Operation (LASSO) and multivariate Cox regression analysis of the EMT-related lncRNA expression data and clinical information. Then, an individualized prognostic prediction model based on the nomogram was developed and the predictive accuracy and discriminative ability of the nomogram were determined by the receiver operating characteristic curve and calibration curve. Finally, a series of analyses, such as functional analysis and unsupervised cluster analysis, were conducted to explore the influence of independent lncRNAs on CRC.

Results: A total of 581 patients were enrolled and an eleven-EMT-related lncRNA risk signature was identified relying on the comprehensive analysis of the EMT-related lncRNA expression data and clinical information in the training cohort. Then, risk scores were calculated to divide patients into high and low-risk groups, and the Kaplan-Meier curve analysis showed that low-risk patients tended to have better overall survival (OS). Multivariate Cox regression analysis indicated that the EMT-related lncRNA signature was significantly associated with prognosis. The results were subsequently confirmed in the validation dataset. Then, we constructed and validated a predictive nomogram for overall survival based on the clinical factors and risk signature. Functional characterization confirmed this signature could predict immune-related phenotype and was associated with immune cell infiltration (i.e., macrophages M0, M1, Tregs, CD4 memory resting cells, and neutrophils), tumor mutation burden (TMB).

Conclusions: Our study highlighted the value of the 11-EMT-lncRNA signature as a predictor of prognosis and immunotherapeutic response in CRC.



中文翻译:

大肠癌 EMT 相关 lncRNA 预后特征的鉴定和验证

背景: 本研究旨在探讨上皮-间质转化(Epithelial-mesenchymal transition)相关的lncRNA在结直肠癌(CRC)中的生物学功能和预后作用。

方法:应用癌症基因组图谱数据库检索基因表达数据和临床信息。依赖于 EMT 相关 lncRNA 表达数据和临床信息的单变量 Cox 回归、最小绝对收缩和选择器操作 (LASSO) 和多变量 Cox 回归分析构建了 EMT 相关 lncRNA 风险特征。然后,建立了基于列线图的个体化预后预测模型,并通过受试者工作特征曲线和校准曲线来确定列线图的预测准确性和判别能力。最后,进行了一系列分析,如功能分析和无监督聚类分析,以探索独立的 lncRNA 对 CRC 的影响。

结果:总共招募了 581 名患者,根据对训练队列中 EMT 相关 lncRNA 表达数据和临床信息的综合分析,确定了 11 个与 EMT 相关的 lncRNA 风险特征。然后,计算风险评分将患者分为高风险组和低风险组,Kaplan-Meier 曲线分析显示低风险患者往往具有更好的总生存期(OS)。多变量 Cox 回归分析表明 EMT 相关的 lncRNA 特征与预后显着相关。结果随后在验证数据集中得到证实。然后,我们根据临床因素和风险特征构建并验证了总体生存率的预测列线图。

结论: 我们的研究强调了 11-EMT-lncRNA 特征作为 CRC 预后和免疫治疗反应预测因子的价值。

更新日期:2021-09-22
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