GPD1L is negatively associated with HIF1α expression and predicts lymph node metastasis in oral and HPV‐ Oropharyngeal cancer
Huan Liu, Shu Wang, Aoming Cheng, Zhengxue Han, Zhien Feng, Chuanbin Guo
Abstract
OBJECTIVE: 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). MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: Low GPD1L + high HIF1α expression can serve as candidate biomarkers for high-risk populations with lymph node metastases in early-stage HNSCC.