Xia Longjie, Lu Jiamin, Qin Yixuan, Huang Runchun, Kong Fanbiao, Deng Yu
Department of Cosmetology and Plastic Surgery Center, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China.
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou, China.
Front Pharmacol. 2024 Sep 23;15:1465586. doi: 10.3389/fphar.2024.1465586. eCollection 2024.
This study was aimed at exploring a specific open region of chromatin in the peripheral blood mononuclear cells (PBMCs) of patients with breast cancer and evaluating its feasibility as a biomarker for diagnosing and predicting breast cancer prognosis. We obtained PBMCs from breast cancer patients and healthy people for the assay for transposase-accessible chromatin (ATAC) sequencing (n = 3) and obtained the GSE27562 chip sequencing data for secondary analyses. Through bioinformatics analysis, we mined the pattern changes for chromatin accessibility in the PBMCs of breast cancer patients. A total of 1,906 differentially accessible regions (DARs) and 1,632 differentially expressed genes (DEGs) were identified via ATAC sequencing. The upregulated DEGs in the disease group were mainly distributed in the cells, organelles, and cell-intima-related structures and were mainly responsible for biological functions such as cell nitrogen complex metabolism, macromolecular metabolism, and cell communication, in addition to functions such as nucleic acid binding, enzyme binding, hydrolase reaction, and transferase activity. Combined with microarray data analysis, the following set of nine DEGs showed intersection between the ATAC and microarray data: JUN, MSL2, CDC42, TRIB1, SERTAD3, RAB14, RHOB, RAB40B, and PRKDC. HOMER predicted and identified five transcription factors that could potentially bind to these peak sites, namely NFY, Sp 2, GFY, NRF, and ELK 1. Chromatin accessibility analysis of the PBMCs from patients with early-stage breast cancer underscores its potential as a significant avenue for biomarker discovery in breast cancer diagnostics and treatment. By screening the transcription factors and DEGs related to breast cancer, this study provides a comprehensive theoretical foundation that is expected to guide future clinical applications and therapeutic developments.
本研究旨在探索乳腺癌患者外周血单个核细胞（PBMCs）中染色质的一个特定开放区域，并评估其作为乳腺癌诊断和预测预后生物标志物的可行性。我们从乳腺癌患者和健康人身上获取PBMCs进行转座酶可及染色质（ATAC）测序分析（n = 3），并获取GSE27562芯片测序数据进行二次分析。通过生物信息学分析，我们挖掘了乳腺癌患者PBMCs中染色质可及性的模式变化。通过ATAC测序共鉴定出1906个差异可及区域（DARs）和1632个差异表达基因（DEGs）。疾病组中上调的DEGs主要分布在细胞、细胞器和细胞内膜相关结构中，除了核酸结合、酶结合、水解酶反应和转移酶活性等功能外，还主要负责细胞氮复合物代谢、大分子代谢和细胞通讯等生物学功能。结合微阵列数据分析，以下一组9个DEGs在ATAC和微阵列数据之间显示出交集：JUN、MSL2、CDC42、TRIB1、SERTAD3、RAB14、RHOB、RAB40B和PRKDC。HOMER预测并鉴定出五个可能与这些峰位点结合的转录因子，即NFY、Sp 2、GFY、NRF和ELK 1。早期乳腺癌患者PBMCs的染色质可及性分析突出了其作为乳腺癌诊断和治疗中生物标志物发现的重要途径的潜力。通过筛选与乳腺癌相关的转录因子和DEGs，本研究提供了一个全面的理论基础，有望指导未来的临床应用和治疗发展。
