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

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.

Abstract

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). 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. 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.

Citation

Joseph, C., Alsaleem, M. A., Toss, M. S., Kariri, Y. A., Althobiti, M., Alsaeed, S., Aljohani, A. I., Narasimha, P. L., Mongan, N. P., Green, A. R., & Rakha, E. A. (2020). The ITIM-Containing Receptor: Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) Modulates Immune Response and Confers Poor Prognosis in Invasive Breast Carcinoma. Cancers, 13(1), 1-19. https://doi.org/10.3390/cancers13010080

• Journal Article Type: Article
• Acceptance Date: Dec 24, 2020
• Online Publication Date: Dec 30, 2020
• Publication Date: Dec 30, 2020
• Deposit Date: Jan 5, 2021
• Publicly Available Date: Jan 6, 2021
• Journal: Cancers
• Electronic ISSN: 2072-6694
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 1
• Article Number: 80
• Pages: 1-19
• DOI: https://doi.org/10.3390/cancers13010080
• Keywords: Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/5184252
• Publisher URL: https://www.mdpi.com/2072-6694/13/1/80