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

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.

• Authors: 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
• Journal: Cancers (Cancers (Basel)) Vol. 13 Issue 1 (Dec 30 2020) ISSN: 2072-6694 [Print] Switzerland
• PMID: 33396670 (Publication Type: Journal Article)