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LEF1/TCF家族成员在乳腺癌中的生物标志物潜力:关于表达及临床意义的生物信息学研究

Biomarker potential of the LEF1/TCF family members in breast cancer: Bioinformatic investigation on expression and clinical significance.

作者信息

Lima Beatriz Miotto, Azevedo Alexandre Luiz Korte de, Giner Igor Samesima, Gomig Talita Helen Bombardelli, Ribeiro Enilze Maria de Souza Fonseca, Cavalli Iglenir João

机构信息

Universidade Federal do Paraná, Departamento de Genética, Curitiba, Paraná, Brasil.

出版信息

Genet Mol Biol. 2023 Dec 15;46(4):e20220346. doi: 10.1590/1678-4685-GMB-2022-0346. eCollection 2023.

Abstract

The LEF1/TCF transcription factor family is related to the development of diverse tissue types, including the mammary tissue, and dysregulation of its expression and function has been described to favor breast tumorigenesis. However, the clinical and biological relevance of this gene family in breast cancer is still poorly understood. Here, we used bioinformatics approaches aiming to reduce this gap. We investigated its expression patterns in molecular and immune breast cancer subtypes; its correlation with immune cell infiltration, and its prognostic values in predicting outcomes. Also, through regulons construction, we determined the genes whose expression is influenced by these transcription factors, and the pathways in which they are involved. We found that LEF1 and TCF3 are over-expressed in breast tumors regarding non-tumor samples, while TCF4 and TCF7 are down-expressed, with the gene's methylation status being associated with its expression dysregulation. All four transcription factors presented significance at the diagnostic and prognostic levels. LEF1, TCF4, and TCF7 presented a significant correlation with immune cell infiltration, being associated with the immune subtypes of less favorable outcomes. Altogether, this research contributes to a more accurate understanding of the expression and clinical and biomarker significance of the LEF1/TCF transcription factors in breast cancer.

摘要

LEF1/TCF转录因子家族与多种组织类型的发育相关,包括乳腺组织,并且其表达和功能的失调被认为有利于乳腺肿瘤的发生。然而,该基因家族在乳腺癌中的临床和生物学相关性仍知之甚少。在此,我们使用生物信息学方法以缩小这一差距。我们研究了其在分子型和免疫型乳腺癌亚型中的表达模式;其与免疫细胞浸润的相关性,以及其在预测预后方面的价值。此外,通过构建调控子,我们确定了其表达受这些转录因子影响的基因,以及它们所涉及的途径。我们发现,与非肿瘤样本相比,LEF1和TCF3在乳腺肿瘤中高表达,而TCF4和TCF7低表达,并且基因的甲基化状态与其表达失调相关。所有这四种转录因子在诊断和预后水平上均具有显著性。LEF1、TCF4和TCF7与免疫细胞浸润呈显著相关,与预后较差的免疫亚型相关。总之,本研究有助于更准确地了解LEF1/TCF转录因子在乳腺癌中的表达以及临床和生物标志物意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a574/10723634/45f12bc8b259/1415-4757-GMB-46-4-e20220346-gf1.jpg

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