EMC8 expression in head and neck squamous cell carcinoma: Implications for poor prognosis and deficient CD8+ T cell infiltration

Abstract

Emerging evidence highlights the role of Endoplasmic Reticulum Membrane Protein Complex (EMC) subunits in tumorigenesis, yet the function of EMC8 (Endoplasmic Reticulum Membrane Protein Complex Subunit 8) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains elusive. In this study, we found EMC8 is significantly upregulated in HNSCC tissues compared to adjacent normal tissues, at both mRNA and protein levels. Kaplan-Meier survival analyses demonstrated that high EMC8 expression is associated with poorer overall survival, disease-specific survival, and progression-free interval in HNSCC patients. Further exploration into the tumor microenvironment showed that EMC8 expression negatively correlates with the infiltration of multiple immune cells, particularly CD8 + T cells, which was validated in clinical samples where high EMC8 expression corresponded to reduced CD8 + T cell infiltration. Additionally, single-cell RNA sequencing data indicated that EMC8 expression is positively associated with dedifferentiation, hypoxia, and stemness properties of HNSCC cells. Collectively, EMC8 upregulation in HNSCC correlates with poor prognosis, reduced CD8 + T cell infiltration, and aggressive phenotypes, positioning it as a potential prognostic marker with mechanistic links to immune evasion and malignancy warranting deeper exploration.