Abstract

BACKGROUND

Identifying reliable prognostic biomarkers and elucidating their cellular origins in the tumor microenvironment (TME) is crucial for improving esophageal squamous cell carcinoma (ESCC) management.

METHODS

Differentially expressed genes were identified from GSE53624 and GSE32424 datasets. LASSO-Cox regression generated a prognostic risk signature, and a nomogram was built for overall survival prediction. CIBERSORT assessed immune infiltration. Experimental validation included qPCR, immunohistochemistry, and functional assays in cell lines and clinical specimens (n = 65). Lysosomal-associated membrane protein 5 (LAMP5)-modified ESCC cells were co-cultured with CD8 + T cells to assess activation and viability. A mouse subcutaneous tumor model was used for in vivo validation.

RESULTS

A four-gene prognostic signature was established; LAMP5 demonstrated the strongest independent prognostic value (area under the curve = 0.773). LAMP5-associated genes were enriched in immune-related pathways. Overexpression of LAMP5 promoted malignant behavior, inhibited ESCC cell apoptosis, and suppressed CD8 + T cell activation. High LAMP5 expression correlated with advanced TNM stage, poor prognosis, and lymph node metastasis. In vivo, LAMP5 overexpression inhibited CD8 + T cell activation and promoted tumor growth.

CONCLUSION

LAMP5 is associated with immune responses in the TME and acts as a promising novel biomarker for ESCC. Its overexpression inhibits CD8 + T cell activation and drives malignant progression.

MeSH

Cells, Genes, Carcinoma, Squamous Cell, Neoplasms, Biomarkers, Esophageal Squamous Cell Carcinoma, Tumor Microenvironment