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6-长链非编码 RNA 评估模型用于监测和预测 HER2 阳性乳腺癌:基于转录组数据。

6-lncRNA Assessment Model for Monitoring and Prognosis of HER2-Positive Breast Cancer: Based on Transcriptome Data.

机构信息

College of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Pathol Oncol Res. 2021 Apr 13;27:609083. doi: 10.3389/pore.2021.609083. eCollection 2021.

Abstract

In view of the high malignancy and poor prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, we analyzed the RNA expression profiles of HER2-positive breast cancer samples to identify the new prognostic biomarkers. The linear fitting method was used to identify the differentially expressed RNAs from the HER2-positive breast cancer RNA expression profiles in the Cancer Genome Atlas (TCGA). Then, a series of methods including univariate Cox, Kaplan-Meier, and random forests, were used to identify the core long non-coding RNAs (lncRNAs) with stable prognostic value for HER2-positive breast cancer. A clinical feature analysis was performed, and a competing endogenous RNA network was constructed to explore the role of these core lncRNAs in HER2-positive breast cancer. In addition, a functional analysis of differentially expressed messenger RNAs in HER-2 positive breast cancer also provided us with some enlightening insights. The high expression of four core lncRNAs (AC010595.1, AC046168.1, AC069277.1, and AP000904.1) was associated with worse overall survival, while the low expression of LINC00528 and MIR762HG was associated with worse overall survival. The 6-lncRNA model has an especially good predictive power for overall survival ( < 0.0001) and 3-year survival (the area under the curve = 0.980) in HER2-positive breast cancer patients. This study provides a new efficient prognostic model and biomarkers of HER2-positive breast cancer. Meanwhile, it also provides a new perspective for elucidating the molecular mechanisms underlying HER2-positive breast cancer.

摘要

鉴于人表皮生长因子受体 2(HER2)阳性乳腺癌的高恶性程度和预后不良,我们分析了 HER2 阳性乳腺癌样本的 RNA 表达谱,以确定新的预后生物标志物。采用线性拟合方法从癌症基因组图谱(TCGA)中的 HER2 阳性乳腺癌 RNA 表达谱中鉴定差异表达的 RNA。然后,使用一系列方法,包括单变量 Cox、Kaplan-Meier 和随机森林,来鉴定具有稳定预后价值的核心长非编码 RNA(lncRNA)。进行临床特征分析,并构建竞争内源性 RNA 网络,以探讨这些核心 lncRNA 在 HER2 阳性乳腺癌中的作用。此外,HER-2 阳性乳腺癌中差异表达信使 RNA 的功能分析也为我们提供了一些启示。四个核心 lncRNA(AC010595.1、AC046168.1、AC069277.1 和 AP000904.1)的高表达与总生存期较差相关,而 LINC00528 和 MIR762HG 的低表达与总生存期较差相关。6-lncRNA 模型对 HER2 阳性乳腺癌患者的总生存期(<0.0001)和 3 年生存率(曲线下面积=0.980)具有特别好的预测能力。这项研究为 HER2 阳性乳腺癌提供了一种新的有效的预后模型和生物标志物。同时,它也为阐明 HER2 阳性乳腺癌的分子机制提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b1/8262145/9316eea1ddf9/pore-27-609083-g001.jpg

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