GPD1L is negatively associated with HIF1α expression and predicts lymph node metastasis in oral and HPV‐ Oropharyngeal cancer

The study is to determine if Glycerol-3-phosphate dehydrogenase 1-like (GPD1L) and hypoxia-inducible factor-1α (HIF1α) can identify high-risk patients with delayed lymph node metastasis in early-stage head and neck squamous cell carcinoma (HNSCC).The mRNA and protein expressions of markers were analyzed using fresh and paraffin embedded HNSCC specimens. The statistical analyses included chi-squared test, t test, correlation analysis, and univariate and multivariate analyses.GPD1L (downregulated) and HIF1α (upregulated) mRNA expression had a negative correlation (r = -.496, p = .001) in cT1-2N0 HNSCC. The low GPD1L + high HIF1α expression group (22.6%) showed a significant decrease in disease-free survival compared with the high GPD1L + low HIF1α expression group (71.4%) in the neck dissection group. The low GPD1L + high HIF1α expression (39.4%) resulted in a significantly higher delayed metastasis rate than the high GPD1L + low HIF1α expression (5.6%) for cT1-2N0 HNSCC in the neck observation group. GPD1L and HIF1α protein expression more accurately predicted lymph node metastasis than the WINTER hypoxia gene panel (false-negative rate in predicting metastasis: 8.1% versus 26.4%). Cox regression analyses found that the combined protein expression of GPD1L and HIF1α could predict delayed metastasis (HR:0.118, 95% CI:0.027-0.525).Low GPD1L + high HIF1α expression can serve as candidate biomarkers for high-risk populations with lymph node metastases in early-stage HNSCC.