HMMR as a robust prognostic biomarker correlates with immune infiltration and cell cycle pathways in oral squamous...

Oral squamous cell carcinoma (OSCC), a prevalent head and neck malignancy with complex molecular pathogenesis and poor prognosis, remains a critical clinical challenge. This study aimed to elucidate the role of hyaluronic acid mediated motility receptor (HMMR) in OSCC progression and evaluate its potential as a diagnostic and prognostic biomarker.

Transcriptomic data was integrated from the TCGA OSCC cohort and two independent GEO cohorts (GSE37991, GSE41613). Differential expression analysis was performed using DESeq2. Common differentially expressed genes (DEGs) were identified via Venn diagram analysis, followed by functional enrichment analysis using the STRING database. Univariate and multivariate Cox regression analyses were conducted with the survival package to identify prognostic markers, and the predictive performance was evaluated by receiver operating characteristic (ROC) analysis. Immune infiltration analysis, pathway enrichment analysis, and protein-protein interaction (PPI) network analysis via GeneMANIA were further applied to explore biological functions.

A total of 2,477 upregulated and 2,214 downregulated differentially expressed genes (DEGs) were identified, with 245 common DEGs pinpointed across datasets. Cluster1 genes were significantly associated with OSCC pathogenesis in functional enrichment. CCNA1, HMMR, and RAG1 were identified as potential prognostic markers, with HMMR demonstrating the strongest predictive value (AUC = 0.919 in ROC analysis). HMMR was significantly overexpressed in OSCC tissues compared to normal controls (P < 0.001), and its high expression correlated with advanced T stage, N stage, pathological grade, shorter disease-specific survival, and disease-free survival. Multivariate analysis confirmed HMMR as an independent prognostic factor for overall survival. Immune infiltration analysis revealed that HMMR expression was positively correlated with 11 immune cell subsets, particularly Th2 cells (r = 0.465) and T helper cells (r = 0.356), suggesting a role in modulating the tumor immune microenvironment. Pathway enrichment linked HMMR to tumor proliferation, hypoxia response, DNA damage repair, and G2/M cell cycle checkpoints. The PPI network analysis identified HMMR-associated complexes involving cell cycle regulators (e.g., CDK1, CCNB1, AURKA), implicating roles in cell cycle regulation, DNA repair, and mitotic progression.

Collectively, this study establishes HMMR as a robust prognostic biomarker for OSCC, tightly associated with malignant progression, immune cell infiltration, and key oncogenic pathways. HMMR and its interacting network represent promising targets for OSCC precision medicine, offering new insights into diagnostic strategies and therapeutic development.