CYSLTR1的表达改变与三阴性乳腺肿瘤的不良临床结果相关:一项计算机方法

Andrés Galindo Céspedes, Mércia Patrícia Ferreira Conceição, Daniel Rodrigues de Bastos, Gabriela Ávila de Grazia, Jean Michel Rocha Sampaio Leite, Renan Gomes do Nascimento, Matthew Thomas Ferreira, Rossana Mendoza Lopez
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引用次数: 0

摘要

目的:三阴性乳腺癌(Triple negative breast cancer, TNBC)由于炎症信号通路失调和肿瘤微环境的显著改变,复发率高,可能影响多种治疗的失败。半胱氨酸白三烯受体1 (CYSLTR1)是炎症的白三烯调节剂,已被证明在癌症的发病和生存中起重要作用,但其在乳腺癌中的作用的研究很少报道。材料和方法:目前的工作是使用公开可用的平台进行的,这些平台具有组学数据,以评估CYSLTR1表达的临床潜力及其在乳腺癌患者大队列样本中的预后验证。选择包含临床信息、RNA-seq和蛋白质数据的网络平台对潜在标记物CYLSTR1进行计算机分析。这些平台包括相关、表达、预后、药物相互作用、基因网络构建等模块。结果:Kaplan-Meier曲线显示,在TNBC数据集上测试时,CYSLTR1水平的降低与总生存期(ppppP2RY10和XCR1)的不利结果相对应。结论:我们的数据强调了CYSLTR1的相关性,因为它可能在TNBC治疗中发挥重要作用。然而,进一步的体外和体内研究应该针对验证我们的发现,以努力提高我们对TNBC病理的理解。
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Altered Expression of CYSLTR1 is Associated With Adverse Clinical Outcome in Triple Negative Breast Tumors: An In Silico Approach.

Objective: Triple negative breast cancer (TNBC) has high relapse rates due to dysregulated inflammatory signaling pathways and significant changes in the tumor microenvironment, probably influencing the failure of several therapies. The Cysteinyl Leukotriene Receptor 1 (CYSLTR1), a leukotriene modulator of inflammation, has been shown to play an important role in cancer pathogenesis and survival but few studies have been reported on its role in breast cancer.

Materials and methods: The present work was conducted using publicly available platforms that have omics data to assess the clinical potential of CYSLTR1 expression and its prognostic validation in large cohorts of samples from breast cancer patients. Web platforms containing clinical information, RNA-seq and protein data were selected to perform in silico analyses of the potential marker CYLSTR1. Added together, the platforms included modules for correlation, expression, prognosis, drug interactions, and construction of gene networks.

Results: Kaplan-Meier curves revealed that reduced levels of CYSLTR1 corresponded to an unfavorable outcome for overall survival (p<0.005) as well as relapse-free survival (p<0.001) in the basal subtype. Additionally, CYSLTR1 was downregulated in breast tumor samples compared to adjacent healthy tissue (p<0.01) and the basal subtype exhibited the lowest expression of CYSLTR1 relative to the other subtypes (p<0.0001). Furthermore, gene networking analysis showed strong associations of CYSLTR1 with two protein-coding genes (P2RY10 and XCR1) when tested on a TNBC dataset.

Conclusion: Our data highlighted the relevance of CYSLTR1 since it may play an important role in TNBC therapy. However, further in vitro and in vivo studies should be directed towards validating our findings in an effort to improve our understanding of TNBC pathology.

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