Moradpoor Raheleh, Zali Hakimeh, Gharebaghian Ahmad, Akbari Mohammad Esmaeil, Ajdari Soheila, Salimi Mona
Department of Basic Sciences, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences,Tehran, Iran.
Cell J. 2021 Sep;23(4):406-413. doi: 10.22074/cellj.2021.7053. Epub 2021 Aug 29.
Breast cancer (BC) still remains an imperative clinical issue, despite advances in the diagnosis, prognosis and treatment modalities of this malignancy. Hence, progress has been made to identify non-invasive, high sensitive and specific biomarkers. Since immune system affects development of breast cancer, peripheral blood mononuclear cells (PBMCs) -a subpopulation of immune cells- can be considered as a promising tool in the field of BC biomarker research. In the current study, we initially attempted to use concept of the present shared biomarkers in solid tumors and systemic immune profile and then evaluate correlation of these biomarkers to clinical use in cancer research.
In this experimental study, available microarray gene expression datasets of BC as well as the related PBMCs were retrieved and downloaded from the Gene Expression Omnibus (GEO) database, followed by analysis using GEO2R along with affylmGUI, a R-based package, to obtain differentially expressed genes (DEGs). Signature genes from 20 types of cancer were also applied to validate DEGs. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was carried out to assess mRNA level of CCNB2 in PBMC of the BC patients and healthy subjects.
DEGs analysis for the transcription profile of BC cells and PBMCs showed two shared targets, CCNB2 and PGK1. Validation with systems biology using reweighted 20 types of cancer signature genes revealed that CCNB2 is the only common target in BC and its related PBMCs, which was further validated by qRT-PCR implying a significant increase in the level of CCNB2 in the BC patients.
Results of this study demonstrated that PBMCs are affected by BC cells and CCNB2 may be of value as a diagnostic biomarker for breast cancer. However, verification would require future detailed experimental plans.
尽管乳腺癌在诊断、预后和治疗方式方面取得了进展,但它仍然是一个至关重要的临床问题。因此,在识别非侵入性、高灵敏度和特异性生物标志物方面已经取得了进展。由于免疫系统会影响乳腺癌的发展,外周血单个核细胞(PBMCs)——免疫细胞的一个亚群——可被视为乳腺癌生物标志物研究领域中一种有前景的工具。在本研究中,我们首先尝试运用实体瘤中当前共享生物标志物的概念以及全身免疫概况,然后评估这些生物标志物与癌症研究临床应用的相关性。
在这项实验研究中,从基因表达综合数据库(GEO)检索并下载了现有的乳腺癌微阵列基因表达数据集以及相关的PBMCs,随后使用GEO2R以及基于R的软件包affylmGUI进行分析,以获得差异表达基因(DEGs)。还应用了20种癌症的特征基因来验证DEGs。进行定量逆转录聚合酶链反应(qRT-PCR)以评估乳腺癌患者和健康受试者外周血单个核细胞中CCNB2的mRNA水平。
对乳腺癌细胞和外周血单个核细胞转录谱的差异表达基因分析显示了两个共同靶点,即CCNB2和PGK1。使用加权的20种癌症特征基因进行系统生物学验证表明,CCNB2是乳腺癌及其相关外周血单个核细胞中唯一的共同靶点,qRT-PCR进一步验证了这一点,这意味着乳腺癌患者中CCNB2水平显著升高。
本研究结果表明外周血单个核细胞受乳腺癌细胞影响,CCNB2可能作为乳腺癌的诊断生物标志物具有价值。然而,验证需要未来详细的实验计划。