Prion protein is associated with a worse prognosis of head and neck squamous cell carcinoma.

Background Head and neck squamous cell carcinoma (HNSC) etiopathogenesis remains unclear, and the biological changes with the activation of heat shock proteins (HSPs) and prion protein (PRNP) promoted by hypoxia in HNSC are undetermined. Objective This study investigates hypoxia's effect in lymph node metastasis by PRNP expression changes and its main partners. Methods The study combined a theoretical/cell culture study with a case-control study. First, bioinformatics and cell culture were performed. A case-control study was performed in a second step by comparing HNSC patients with and without lymph node metastasis. Analyses The Cancer Genome Atlas (TCGA) data source validate the theory in the global population study. Results Bioinformatics analysis suggests that hypoxia-inducible factor-1α (HIF1A) is associated with HSPA4, HSP90AA1, and PRNP expression. TCGA data validate the hypothesis that higher HSP90AA1, HSPA4, and PRNP are related to metastases and low survival. Herein, the cell study demonstrated that muted PRNP did not respond to hypoxia. Conclusions Our results collectively provide the first evidence that PRNP promotes HNSC lymph node metastasis progression through the upregulation of HSPA4, HSP90AA1, and HIF1A. Our findings may provide a molecular basis for the promoting Role of PRNP in HNSC progression.