Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar-190006, J&K India.
Department of Medical Laboratory Sciences, CAMS, Majmaah University, Almajmaah, KSA.
Clin Breast Cancer. 2022 Aug;22(6):567-578. doi: 10.1016/j.clbc.2022.04.008. Epub 2022 Apr 25.
Breast cancer (BC), one of the most prevalent malignancies, is the second major cause of mortality from cancer among women worldwide. Even though substantial progress has been made in breast cancer treatment, metastasis still accounts for the majority of the deaths. The tumor microenvironment (TME) comprising stromal and non-stromal components is central to tumor growth and development and is partly regulated by chemokines. Chemokines regulate immune cell trafficking, the development of stroma and play a key role in inflammation, a cancer hallmark.
In the present study, we used a bioinformatics approach to identify highly deregulated chemokines in BC patients. We performed expression analysis, survival analysis, gene ontology analysis, KEGG analysis, and protein-protein interaction network analysis of the deregulated chemokines using Gepia2, UALCAN, Kaplan-Meier Plotter, DAVID, and STRING tools.
We identified >2-fold change (FC) increase in CXCL9/10/11/13 and >-2 FC decrease in CCL14/21/28, CXCL2/12 CX3CL1. Also, increased expression of CCL14, CCL21, CXCL13, CXCL9, CXCL12 correlated with better overall survival (OS) of BC patients.
Our results strongly indicate that chemokines may have potential biomarker characteristics, and the constructed PPI network contributed to an in-depth understanding of the chemokine networks. The deregulated chemokines may prove to be therapeutic targets for the effective management of BC.
乳腺癌(BC)是最常见的恶性肿瘤之一,是全球女性癌症死亡的第二大主要原因。尽管在乳腺癌治疗方面取得了重大进展,但转移仍然是大多数死亡的原因。由基质和非基质成分组成的肿瘤微环境(TME)是肿瘤生长和发展的核心,部分受趋化因子调节。趋化因子调节免疫细胞的迁移、基质的发育,并在炎症中发挥关键作用,炎症是癌症的一个标志。
在本研究中,我们使用生物信息学方法来鉴定 BC 患者中高度失调的趋化因子。我们使用 Gepia2、UALCAN、Kaplan-Meier Plotter、DAVID 和 STRING 工具对失调的趋化因子进行表达分析、生存分析、基因本体论分析、KEGG 分析和蛋白质-蛋白质相互作用网络分析。
我们发现 CXCL9/10/11/13 的倍数变化(FC)增加了>2 倍,CCL14/21/28 的 FC 减少了>-2,CXCL2/12 CX3CL1。此外,CCL14、CCL21、CXCL13、CXCL9 和 CXCL12 的表达增加与 BC 患者的总体生存(OS)更好相关。
我们的结果强烈表明,趋化因子可能具有潜在的生物标志物特征,构建的 PPI 网络有助于深入了解趋化因子网络。失调的趋化因子可能被证明是有效管理 BC 的治疗靶点。