Thyroid and Breast Department III, Cangzhou Central Hospital, Cangzhou, Hebei, China.
Ultrasound Department II, Cangzhou Central Hospital, Cangzhou, Hebei, China.
Cell Biol Int. 2020 Oct;44(10):2002-2010. doi: 10.1002/cbin.11406. Epub 2020 Jul 1.
Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. The aim of this study is to identify the diagnostic and poor prognostic signatures in TNBC by exploring the aberrant DNA methylation and gene expression. Differential expression and methylation analysis of the TNBC and paracancer samples from The Cancer Genome Atlas were performed. Gene set enrichment and protein-protein interaction (PPI) network analysis was used to explore the mechanisms of TNBC. Methylation-gene expression correlation analysis was performed, and multivariate Cox analysis and receiver operating characteristics analysis were used to further screen the hub genes for TNBC. We identified 1,525 differentially expressed genes and 150 differentially methylated genes between TNBC and paracancer samples. About 96.64% of the methylation sites were located on the CpG island. A total of 17 Gene Ontology biological process terms and 18 signal pathways were significantly enriched. GNG4, GNG11, PENK, MAOA, and AOX1 were identified as the core genes of the PPI network. Methylation-expression correlations revealed that ABCC9 (cg06951626), NKAPL (cg18675097, cg01031101, and cg17384889), and TMEM132C (cg03530754) showed promise as diagnostic and prognostic markers in TNBC. ABCC9 (cg06951626), NKAPL (cg18675097, cg01031101, and cg17384889), and TMEM132C (cg03530754) were potential diagnostic and prognostic markers in TNBC.
三阴性乳腺癌（TNBC）是一种高度异质性的疾病。本研究旨在通过探索异常的 DNA 甲基化和基因表达，鉴定 TNBC 的诊断和预后不良标志物。对来自癌症基因组图谱的 TNBC 和配对癌旁样本进行了差异表达和甲基化分析。采用基因集富集和蛋白质-蛋白质相互作用（PPI）网络分析探讨 TNBC 的机制。进行了甲基化-基因表达相关性分析，并进行了多变量 Cox 分析和受试者工作特征分析，以进一步筛选 TNBC 的枢纽基因。我们在 TNBC 和配对癌旁样本之间鉴定出 1525 个差异表达基因和 150 个差异甲基化基因。大约 96.64%的甲基化位点位于 CpG 岛上。共鉴定到 17 个 GO 生物学过程术语和 18 个信号通路显著富集。GNG4、GNG11、PENK、MAOA 和 AOX1 被确定为 PPI 网络的核心基因。甲基化-表达相关性表明，ABCC9（cg06951626）、NKAPL（cg18675097、cg01031101 和 cg17384889）和 TMEM132C（cg03530754）作为 TNBC 的诊断和预后标志物具有潜力。ABCC9（cg06951626）、NKAPL（cg18675097、cg01031101 和 cg17384889）和 TMEM132C（cg03530754）是 TNBC 的潜在诊断和预后标志物。
