Joseph Chitra, Alsaleem Mansour A, Toss Michael S, Kariri Yousif A, Althobiti Maryam, Alsaeed Sami, Aljohani Abrar I, Narasimha Pavan L, Mongan Nigel P, Green Andrew R, Rakha Emad A
School of Medicine, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham NG7 2RD, UK.
Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.
Cancers (Basel). 2020 Dec 30;13(1):80. doi: 10.3390/cancers13010080.
The leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) plays a role in immune response homeostasis, extracellular matrix remodelling and it is overexpressed in many high-grade cancers. This study aimed to elucidate the biological and prognostic role of LAIR-1 in invasive breast cancer (BC).
The biological and prognostic effect of LAIR-1 was evaluated at the mRNA and protein levels using well-characterised multiple BC cohorts. Related signalling pathways were evaluated using in silico differential gene expression and siRNA knockdown were used for functional analyses.
High LAIR-1 expression either in mRNA or protein levels were associated with high tumour grade, poor Nottingham Prognostic Index, hormone receptor negativity, immune cell infiltrates and extracellular matrix remodelling elements. High LAIR-1 protein expression was an independent predictor of shorter BC-specific survival and distant metastasis-free survival in the entire BC cohort and human epidermal growth factor receptor 2 (HER2)+ subtype. Pathway analysis highlights LAIR-1 association with extracellular matrix remodelling-receptor interaction, and cellular proliferation. Depletion of LAIR-1 using siRNA significantly reduced cell proliferation and invasion capability in HER2+ BC cell lines.
High expression of LAIR-1 is associated with poor clinical outcome in BC. Association with immune cells and immune checkpoint markers warrant further studies to assess the underlying mechanistic roles.
白细胞相关免疫球蛋白样受体-1（LAIR-1）在免疫反应稳态、细胞外基质重塑中发挥作用，且在许多高级别癌症中过度表达。本研究旨在阐明LAIR-1在浸润性乳腺癌（BC）中的生物学及预后作用。
使用特征明确的多个乳腺癌队列，在mRNA和蛋白质水平评估LAIR-1的生物学及预后作用。使用计算机差异基因表达评估相关信号通路，并使用小干扰RNA（siRNA）敲低进行功能分析。
LAIR-1在mRNA或蛋白质水平的高表达与高肿瘤分级、不良诺丁汉预后指数、激素受体阴性、免疫细胞浸润及细胞外基质重塑成分相关。在整个乳腺癌队列及人表皮生长因子受体2（HER2）阳性亚型中，LAIR-1蛋白高表达是较短的乳腺癌特异性生存期及无远处转移生存期的独立预测因素。通路分析突出了LAIR-1与细胞外基质重塑-受体相互作用及细胞增殖的关联。使用siRNA敲低LAIR-1可显著降低HER2阳性乳腺癌细胞系的细胞增殖及侵袭能力。
LAIR-1高表达与乳腺癌不良临床结局相关。与免疫细胞及免疫检查点标志物的关联值得进一步研究以评估其潜在的机制作用。
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