Prognostic and diagnostic evaluation of HSPG2 gene expression in oral squamous cell carcinoma: A case-control study

This study aimed to evaluate HSPG2 expression in oral squamous cell carcinoma (OSCC) and validate its clinical relevance using external datasets, including The Cancer Genome Atlas (TCGA) and the single-cell GSE103322 dataset.

A matched case-control study (2022-2024) enrolled 25 OSCC patients and 25 age- and sex-matched healthy controls, also balanced for smoking and alcohol status. Biological samples (formalin-fixed paraffin-embedded tissue, blood plasma, and saliva) were collected. RNA was extracted, converted to cDNA, and HSPG2 expression quantified using qRT-PCR. External validation was performed using TCGA, and single-cell analysis utilized GSE103322. Receiver operating characteristic (ROC) curves assessed diagnostic performance.

HSPG2 expression was significantly elevated in OSCC tissues (p = 0.002) and blood plasma (p = 0.02), but not in saliva (p = 0.58). Increased expression was observed across genders, all age groups, tumor stages, and grades, and was independent of HPV status. TCGA analysis confirmed higher HSPG2 expression in tumors versus normal tissues across demographic and clinical subgroups, with high expression associated with poorer survival, particularly among African American patients. Single-cell RNA-seq revealed stromal enrichment of HSPG2, predominantly in endothelial cells and fibroblasts. ROC analysis demonstrated good diagnostic performance in tissue (AUC = 0.86) and blood plasma (AUC = 0.84), but limited value in saliva (AUC = 0.57).

HSPG2 is overexpressed in OSCC tissues and plasma, correlating with tumor stage, grade, and poor survival, especially in African Americans. As a stromal-associated gene promoting tumor progression, HSPG2 holds promise as a diagnostic and prognostic biomarker in OSCC.