Unveiling LAIR1: a prognostic biomarker associated with gastric cancer progression and metastasis

The role of leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) in immune regulation has been documented, yet its function in gastric cancer (GC) pathogenesis is not well defined. This study sought to evaluate the prognostic relevance and biological influence of LAIR1 in GC development and dissemination.

We employed multi-database bioinformatics to examine LAIR1 expression patterns and their relationship with clinical outcomes. Validation was performed using 177 clinical GC specimens through immunohistochemistry (IHC), western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). Functional effects of LAIR1 on malignant behaviors were assessed using in vitro experiments, including Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays. Multiple murine models-subcutaneous xenograft, peritoneal dissemination, pulmonary metastasis, and lymph node metastasis-were utilized to examine tumor growth and metastatic potential in vivo.

LAIR1 was markedly upregulated in GC tissues and associated with adverse clinicopathological characteristics, such as poor differentiation, advanced T and N stage, lymph node metastasis, and reduced patient survival. In vitro, LAIR1 depletion attenuated GC cell proliferation, migration, and invasion, whereas its overexpression enhanced these phenotypes. Consistently, LAIR1 knockdown impeded tumor growth and metastasis across all in vivo models. Mechanistic analyses indicated a correlation between LAIR1 expression and epithelial-mesenchymal transition (EMT), characterized by elevated Snail1 and N-cadherin and reduced E-cadherin levels.

LAIR1 represents a novel prognostic indicator and functional oncoprotein that facilitates GC progression and metastasis, possibly through modulation of the EMT pathway. These findings underscore its potential as a therapeutic target in GC.