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

• Published in: Journal of oral pathology & medicine 2021-11, Vol.50 (10), p.985-994
• Main Authors: Santos, Eloa Mangabeira, Fraga, Carlos Alberto de Carvalho, Xavier, Alessandra Rejane Ericsson de Oliveira, Xavier, Mauro Aparecido de Souza, Souza, Marcela Gonçalves, Jesus, Sabrina Ferreira de, Paula, Alfredo Maurício Batista de, Farias, Lucyana Conceição, Santos, Sérgio Henrique Sousa, Santos, Tiago Goss, Beraldo, Flavio H., Guimarães, André Luiz Sena
• Format: Article
• Language: English
• Subjects: a biological marker; Bioinformatics; Biomarkers, Tumor - genetics; Case-Control Studies; Cell culture; Cell survival; Genomes; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - genetics; Heat shock proteins; HSP70; HSP90; Humans; Hypoxia; Lymph nodes; Lymphatic system; Medical prognosis; Metastases; Metastasis; Population studies; prion; Prion protein; Prion Proteins - genetics; Prognosis; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - genetics; treatment
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.13188

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. 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 validates 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. Discussion 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.