Research on the Expression and Mechanism of LRRC8D in Esophageal Squamous Cell Carcinoma

Purpose The leucine-rich repeat-containing 8 (LRRC8) protein family, particularly leucine-rich repeat containing 8 family, member D (LRRC8D), has been implicated in various cancers. However, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to evaluate LRRC8D as a potential diagnostic biomarker for ESCC and to elucidate its regulatory mechanisms. Materials and methods The expression of LRRC8D in ESCC was analyzed using publicly available datasets, in-house RNA sequencing data, and immunohistochemistry. Associations between LRRC8D expression and clinical features were assessed using RStudio 4.3.2. Immune cell infiltration and its relationship with LRRC8D were investigated using the CIBERSORT R package. Kaplan-Meier survival analysis evaluated the prognostic relevance of LRRC8D. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and protein-protein interaction (PPI) networks construction, were performed to identify core genes and pathways associated with LRRC8D. Results LRRC8D expression at both the mRNA and protein levels was significantly upregulated in ESCC tissues compared to non-cancerous tissues. While LRRC8D expression did not correlate with clinical characteristics such as age, gender, or tumor stage, it was significantly associated with immune cell composition in the tumor microenvironment. Survival analysis revealed no significant relationship between LRRC8D expression and patient outcomes, although higher expression levels showed a trend toward improved survival. Functional network analyses identified core genes associated with LRRC8D that play key roles in cell cycle regulation and mitosis. Enrichment analyses further highlighted LRRC8D's involvement in the cell cycle and related signaling pathways. Conclusion LRRC8D is a promising diagnostic biomarker for distinguishing ESCC tissues from non-cancerous tissues but lacks significant prognostic value. Its expression is closely associated with immune cell dynamics in ESCC and may influence tumor phenotypes through cell cycle regulation.