Liu Min, Mo Fei, Song Xiaohan, He Yun, Yuan Yan, Yan Jiaoyan, Yang Ye, Huang Jian, Zhang Shu
Department of Laboratory Medicine, Sichuan Maternal and Child Health Hospital, Chengdu, Sichuan Province, China.
Department of Clinical Laboratory, Affiliated Hospital of Guizhou Medical UniversityGuiyang, Guizhou Province, China.
PeerJ. 2021 Sep 17;9:e12147. doi: 10.7717/peerj.12147. eCollection 2021.
Breast cancer (BC) is characterized by concealed onset, delayed diagnosis, and high fatality rates making it particularly dangerous to patients' health. The purpose of this study was to use comprehensive bioinformatics analysis and experimental verification to find a new biomarker for BC diagnosis.
We comprehensively analyzed microRNA (miRNA) and mRNA expression profiles from the Gene Expression Omnibus (GEO) and screened out differentially-expressed (DE) miRNAs and mRNAs. We used the miRNet website to predict potential DE-miRNA target genes. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID), we performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on overlapping potential target genes and DE-mRNAs. The protein-protein interaction (PPI) network was then established. The miRNA-mRNA regulatory network was constructed using Cytoscape and the analysis results were visualized. We verified the expression of the most up-regulated DE-miRNA using reverse transcription and a quantitative polymerase chain reaction in BC tissue. The diagnostic value of the most up-regulated DE-miRNA was further explored across three levels: plasma-derived exosomes, cells, and cell exosomes.
Our comprehensive bioinformatics analysis and experimental results showed that hsa-miR-21-5p was significantly up-regulated in BC tissue, cells, and exosomes. Our results also revealed that tumor-derived hsa-miR-21-5p could be packaged in exosomes and released into peripheral blood. Additionally, when evaluating the diagnostic value of plasma exosomal hsa-miR-21-5p, we found that it was significantly up-regulated in BC patients. Receiver operating characteristic (ROC) analysis also confirmed that hsa-miR-21-5p could effectively distinguish healthy people from BC patients. The sensitivity and specificity were 86.7% and 93.3%, respectively.
This study's results showed that plasma exosomal hsa-miR-21-5p could be used as a biomarker for BC diagnosis.
乳腺癌具有发病隐匿、诊断延迟和死亡率高的特点，对患者健康构成特别危险。本研究的目的是通过综合生物信息学分析和实验验证，寻找一种用于乳腺癌诊断的新生物标志物。
我们全面分析了来自基因表达综合数据库（GEO）的 microRNA（miRNA）和 mRNA 表达谱，筛选出差异表达（DE）的 miRNA 和 mRNA。我们使用 miRNet 网站预测潜在的 DE-miRNA 靶基因。利用注释、可视化和综合发现数据库（DAVID），我们对重叠的潜在靶基因和 DE-mRNA 进行了基因本体（GO）和京都基因与基因组百科全书（KEGG）分析。然后建立了蛋白质-蛋白质相互作用（PPI）网络。使用 Cytoscape 构建 miRNA-mRNA 调控网络并将分析结果可视化。我们在乳腺癌组织中使用逆转录和定量聚合酶链反应验证了上调最显著的 DE-miRNA 的表达。在血浆来源的外泌体、细胞和细胞外泌体三个水平上进一步探索上调最显著的 DE-miRNA 的诊断价值。
我们的综合生物信息学分析和实验结果表明，hsa-miR-21-5p 在乳腺癌组织、细胞和外泌体中显著上调。我们的结果还显示，肿瘤来源的 hsa-miR-21-5p 可以被包装在外泌体中并释放到外周血中。此外，在评估血浆外泌体 hsa-miR-21-5p 的诊断价值时，我们发现它在乳腺癌患者中显著上调。受试者工作特征（ROC）分析也证实，hsa-miR-21-5p 可以有效地区分健康人和乳腺癌患者。敏感性和特异性分别为 86.7%和 93.3%。
本研究结果表明，血浆外泌体 hsa-miR-21-5p 可作为乳腺癌诊断的生物标志物。
