探索乳腺癌相关的上皮间充质转化相关长链非编码RNA(lncRNA)签名和药物敏感性。
Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer.
发表日期:2023
作者:
Chengxin Li, Lewei Zheng, Gaoran Xu, Qianqian Yuan, Ziyang Di, Yalong Yang, Xingxing Dong, Jinxuan Hou, Gaosong Wu
来源:
Frontiers in Endocrinology
摘要:
乳腺癌(BRCA)已成为全球女性最常被诊断的癌症,严重威胁女性健康。上皮-间质转变(EMT)过程与BRCA患者的转移和耐药性相关。然而,EMT相关的lncRNA在BRCA中的预后价值仍需揭示。本研究旨在构建一种具有准确预测能力的EMT相关lncRNA(ERL)签名,用于评估BRCA患者的预后。在研究中使用了来自TCGA(癌症基因组图谱)的RNA-seq表达数据和临床特征。首先,我们通过Pearson相关性分析确定了EMT相关的lncRNA。采用单变量Cox回归和Lasso惩罚的Cox回归分析构建了一个EMT相关lncRNA预后风险签名。使用Kaplan-Meier(KM)生存分析、ROC曲线和C-index来验证该模型的性能。最后,我们构建了一个用于评估BRCA患者的临床实践中的一项评分表,并通过校准曲线和决策曲线分析(DCA)进行验证。我们还评估了签名lncRNA的药物敏感性和乳腺癌中的肿瘤免疫细胞浸润。我们基于与EMT过程相关的lncRNA构建了一个10-lncRNA风险评分签名。根据中位数风险评分,我们可以将BRCA患者分为高风险组和低风险组。预后风险签名表现出极高的准确性,并且显示出与其他临床特征足够独立的特性。免疫细胞浸润分析显示,预后风险签名与免疫细胞亚型的浸润有关。药物敏感性分析证明ERL签名能够有效预测BRCA患者对常见化疗药物的敏感性,并为高风险和低风险患者提供化疗药物的指导。我们的ERL签名和评分表在预后方面具有很高的价值,并可以成为临床指导的可靠工具。版权所有 © 2023 李,郑,徐,袁,迪,杨,董,侯和吴。
Breast cancer (BRCA) has become the most diagnosed cancer worldwide for female and seriously endanger female health. The epithelial-mesenchymal transition (EMT) process is associated with metastasis and drug resistance in BRCA patients. However, the prognostic value of EMT-related lncRNA in BRCA still needs to be revealed. The aim of this study is to construct an EMT-related lncRNA (ERL) signature with accuracy predictive ability for the prognosis of BRCA patients.RNA-seq expression data and Clinical characteristics obtained from the TCGA (The Cancer Genome Atlas) were used in the study. First, we identified the EMT-related lncRNA by the Pearson correlation analysis. An EMT-related lncRNAs prognostic risk signature was constructed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model's performance was validated using Kaplan-Meier (KM) survival analysis, ROC curve and C-index. Finally, a nomogram was constructed for clinical practice in evaluating the patients with BRCA and validated by calibration curve and decision curve analysis (DCA). We also evaluated the drug sensitivity of signature lncRNA and the tumor immune cell infiltration in breast cancer.We constructed a 10-lncRNA risk score signature based on the lncRNAs associated with the EMT process. We could assign BRCA patients to the high- and low-risk group according to the median risk score. The prognostic risk signature showed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of the immune cell subtype. Drug sensitivity analysis proved ERLs signature could effectively predict the sensitivity of patients to common chemotherapy drugs in BRCA and provide guidance for chemotherapy drugs for high-risk and low-risk patients.Our ERL signature and nomogram have excellent prognostic value and could become reliable tools for clinical guidance.Copyright © 2023 Li, Zheng, Xu, Yuan, Di, Yang, Dong, Hou and Wu.