Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
J Cell Biochem. 2020 Jul;121(7):3537-3546. doi: 10.1002/jcb.29633. Epub 2019 Dec 30.
Breast cancer is a malignant tumor that seriously threatens women's health, and luminal-like cancer subtypes account for the majority of the cases. The purpose of this study was to investigate the relationships among DNA methylation, gene expression profile, and the tumor-immune microenvironment of luminal-like breast cancer, and to identify the potential key genes that regulate immune cell infiltration in luminal-like breast cancer. The ESTIMATE algorithm was applied to calculate immune scores and stromal scores of patients with breast cancer. Kaplan-Meier curves were generated for survival analysis. The clusterProfile package was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Correlations between ADCY6 expression and immune cell infiltration-related pathways were analyzed by gene set variation analysis. R software was used for the statistical analysis and figure generation. Disease-free survival was higher in the immune score-high group than it was in the immune score-low group, while the stromal score had no correlation with prognosis. There were 515 genes that differed in both gene expression and DNA methylation levels, and these genes were mainly enriched in immune process-related pathways. ADCY6 was enriched in module A of the PPI network. Patients with downregulation and hypermethylation of ADCY6 associated with a better prognosis. ADCY6 expression was negatively correlated with the activation of immune process-related signaling pathways, immune checkpoint receptors, and ligands, except for CLEC4G. DNA methylation was found to be involved in the regulation of the key cellular pathways of luminal-like breast cancer immune cell infiltration. Additionally, ADCY6 was identified as a prognostic factor involved in the DNA methylation-regulated immune processes in luminal-like breast cancer.
乳腺癌是一种严重威胁女性健康的恶性肿瘤，其中管腔样癌亚型占多数。本研究旨在探讨管腔样乳腺癌中 DNA 甲基化、基因表达谱与肿瘤免疫微环境的关系，并鉴定调控管腔样乳腺癌免疫细胞浸润的潜在关键基因。采用 ESTIMATE 算法计算乳腺癌患者的免疫评分和基质评分，绘制 Kaplan-Meier 曲线进行生存分析。使用 clusterProfile 包进行基因本体论和京都基因与基因组百科全书分析。利用 STRING 数据库和 Cytoscape 软件构建蛋白质-蛋白质相互作用（PPI）网络。通过基因集变异分析分析 ADCY6 表达与免疫细胞浸润相关通路的相关性。使用 R 软件进行统计分析和图形生成。免疫评分高的患者无病生存率高于免疫评分低的患者，而基质评分与预后无关。有 515 个基因在基因表达和 DNA 甲基化水平上均存在差异，这些基因主要富集在免疫过程相关通路中。ADCY6 富集在 PPI 网络的模块 A 中。ADCY6 下调和高甲基化与更好的预后相关。ADCY6 表达与免疫过程相关信号通路、免疫检查点受体和配体的激活呈负相关，除 CLEC4G 外。DNA 甲基化参与调节管腔样乳腺癌免疫细胞浸润的关键细胞通路。此外，ADCY6 被鉴定为与管腔样乳腺癌中 DNA 甲基化调控免疫过程相关的预后因素。
