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一种用于识别胃癌中 DNA 甲基化与基因表达水平之间关系以及预测预后的稀疏低秩回归模型。

A Sparse and Low-Rank Regression Model for Identifying the Relationships Between DNA Methylation and Gene Expression Levels in Gastric Cancer and the Prediction of Prognosis.

机构信息

School of Mathematics and Physics, University of Science & Technology Beijing, Beijing 100083, China.

School of Mathematics and Statistics, Qingdao University, Qingdao 266003, China.

出版信息

Genes (Basel). 2021 Jun 2;12(6):854. doi: 10.3390/genes12060854.

Abstract

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.

摘要

DNA 甲基化是基因表达的重要调控因子,它可以影响肿瘤异质性,并且在不同基因中的表达水平较弱且变化。胃癌(GC)是一种消化系统高度异质性的癌症,全球死亡率很高。GC 的异质亚型导致不同的预后。在这项研究中,我们通过引入基于来自癌症基因组图谱数据库的 375 个肿瘤样本和 32 个正常样本的 GC 数据集的稀疏低秩回归模型,探讨了 DNA 甲基化与基因表达水平之间的关系。发现 DNA 甲基化水平和位点的差异与与 GC 发展相关的差异表达基因有关。总体而言,发现 29 个甲基化驱动基因与 GC 亚型有关,在预后模型中,我们探讨了与甲基化位点相关的五个预后。最后,基于低秩矩阵,确定了七个具有不同甲基化状态的亚组。这些基于 DNA 甲基化水平的特定分类可能有助于解释异质性并有助于个性化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9fc/8228406/355893b6e544/genes-12-00854-g001.jpg

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