Clinical Significance of LRG1 Protein Expression in Locally Advanced Gastric Cancer After Curative Resection

Background/Aim: Leucine-rich α2-glycoprotein-1 (LRG1), a secreted glycoprotein involved in inflammation, angiogenesis, and tumor progression, has been proposed as a biomarker in several malignancies. However, its clinical relevance in gastric cancer (GC), particularly in curatively resected locally advanced disease, remains unclear. This study aimed to evaluate the prognostic significance of tumoral LRG1 protein expression in patients with pathological stage (pStage) II/III GC after R0 resection.

Patients and Methods: A total of 508 patients with pStage II/III GC who underwent R0 gastrectomy with D2 or more extensive lymphadenectomy between 2011 and 2020 were retrospectively analyzed. Tissue microarrays were constructed from three representative tumor regions (tumor center, peripheral area, and invasive front). LRG1 expression in tumor cells was examined by immunohistochemistry and quantified using AI-assisted digital image analysis (HALO^®). Patients were classified into high or low LRG1 expression groups according to the median proportion (42%) of moderately/strongly positive tumor cells. Associations between LRG1 expression, clinicopathological factors, and overall survival (OS) were assessed.

Results: High tumoral LRG1 expression was significantly associated with male sex and poorer prognosis. The 5-year OS rate was significantly lower in the high LRG1 group than in the low LRG1 group (57.5% vs. 68.7%, p=0.0085). In multivariate Cox regression analysis, high LRG1 expression remained an independent adverse prognostic factor for OS (HR=1.472; 95% CI=1.013-2.141; p=0.042).

Conclusion: High LRG1 protein expression in primary tumor cells is an independent predictor of poor survival in patients with pStage II/III GC after curative resection. Quantitative assessment of tumoral LRG1 may serve as a useful prognostic biomarker for risk stratification in locally advanced GC.