The ITIM-Containing Receptor: Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) Modulates Immune Response and Confers Poor Prognosis in Invasive Breast Carcinoma

含 ITIM 的受体:白细胞相关免疫球蛋白样受体-1 (LAIR-1) 调节免疫反应并导致浸润性乳腺癌预后不良

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作者:Chitra Joseph, Mansour A Alsaleem, Michael S Toss, Yousif A Kariri, Maryam Althobiti, Sami Alsaeed, Abrar I Aljohani, Pavan L Narasimha, Nigel P Mongan, Andrew R Green, Emad A Rakha

Background

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).

Conclusion

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.

Methods

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.

Results

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.

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