Predictive and mechanistic insights of GLTP on survival in patients with head and neck squamous cell carcinoma

Glycolipid transfer protein (GLTP) is a key regulator of glycosphingolipid distribution between intracellular membranes. Although aberrant GLTP expression has been implicated in various cancers, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear.

HNSCC samples from The Cancer Genome Atlas (TCGA) were stratified based on GLTP expression levels. A comprehensive bioinformatic analysis was conducted to investigate GLTP's expression, functional networks, and impact on the tumor immune microenvironment. To construct a prognostic model, a signature based on genes associated with GLTP expression was developed using univariate Cox and LASSO regression analyses, and its robustness was validated in the independent GSE41613 cohort. The role of GLTP in cell migration was further verified using wound-healing assays in HSC-3 and SCC-9 cell lines with GLTP overexpression or knockdown.

GLTP was significantly downregulated in HNSCC tissues. Functional analysis linked GLTP to epidermal differentiation, muscle contractile processes, and immunomodulatory mechanisms, with involvement in key pathways such as the chemokine, Ras, and PI3K-Akt signaling pathways. Immune infiltration analysis revealed that, compared to the low GLTP expression group, the high GLTP expression group exhibited increased plasma cell infiltration, decreased levels of resting CD4⁺ memory T cells and M1 macrophages, and generally lower expression of immune checkpoint genes. Based on these findings, a GLTP-related risk score model was constructed, which stratified patients into distinct prognostic groups and was validated in an independent cohort. Functional experiments demonstrated that GLTP overexpression inhibited cell migration, whereas its knockdown promoted migration, suggesting that GLTP regulates HNSCC cell motility.

This study developed and validated a GLTP-based prognostic model that stratifies HNSCC patients into distinct risk groups. Functional experiments demonstrated that GLTP overexpression inhibited HNSCC cell migration, while its knockdown enhanced migration. These findings indicate that GLTP is involved in HNSCC progression and provide a rationale for further investigation.