Comprehensive Analysis Identifies FCER1A as a Potential Link Between Immune Dysregulation and Therapeutic Responses in Systemic Lupus Erythematosus and Gastric Cancer

INTRODUCTION: Systemic lupus erythematosus (SLE) patients exhibit an elevated risk of gastric cancer (GC), yet the molecular mechanisms underlying this comorbidity remain poorly understood. This study presents a novel integrative bioinformatics framework to identify shared molecular signatures between SLE and GC and to assess their prognostic implications. METHODS: This study retrieved microarray data from the GSE50772 and GSE81622 datasets in the GEO database and RNA-seq data from the GC cohort in TCGA. Following screening, this study identified differentially expressed genes (DEGs) and further characterized them based on their differential expression. This study identified the common DEGs (co-DEGs) and performed GO and KEGG pathway analyses to identify relevant pathways, immune infiltration, and gene diagnostic value in the context of SLE and GC. RESULTS: By analyzing three independent datasets (GSE50772, GSE81622, and TCGA_STAD), this study identified 12 co-DEGs, among which FCER1A was validated as an independent prognostic factor for GC through multivariate Cox regression (HR = 1.184, P = 0.026). In addition, FCER1A expression showed significant positive correlations with infiltration of multiple immune cell types, including macrophages (P = 3.38e-27, r = 0.52, 95% CI: 0.44-0.59), CD4+ T cells (P = 7.32e-18, r = 0.43, 95% CI: 0.34-0.51), and neutrophils (P = 5.82e-12, r = 0.35, 95% CI: 0.25-0.43), suggesting its role in shaping the tumor immune microenvironment. Kaplan-Meier analysis confirmed that high FCER1A expression predicted poorer overall survival (P = 0.036) and first progression (P = 0.029). DISCUSSION: In this study, FCER1A was identified as the key gene affected by the combination of SLE and GC. CONCLUSION: This study is the first to systematically link FCER1A-mediated immune infiltration to prognosis in SLE-associated GC, offering a potential biomarker and therapeutic target for this understudied comorbidity.