Mohsen Ahmadi: Student Research Committee, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. ORCID
Maryam Eftekhari Kenzerki: Student Research Committee, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Seyed Mohammad Akrami: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Iran.
Salar Pashangzadeh: Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Iran.
Fatemeh Hajiesmaeili: Division of Medical Genetics, Booali Medical Diagnostic Laboratory, Qom, Iran.
Sahereh Rahnavard: Department of Cellular and Molecular Biology, Ahar Branch, Islamic Azad University, Ahar, Iran.
Leila Habibipour: Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Negin Saffarzadeh: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Iran.
Pegah Mousavi: Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Hypoxanthine phosphoribosyltransferase (HPRT1), as a salvage pathway enzyme, plays a crucial role in modulating the cell cycle and has been reported to be overexpressed in multiple cancers. Nevertheless, the relationship between the HPRT1 gene and head and neck squamous cell carcinomas (HNSCCs) has not been investigated so far. In this study, we first evaluated the expression and clinical value of HPRT1 mRNA and protein in tumor and healthy control tissues. Then, we examined mutations of the HPRT1 gene and their association with survival outcomes of patients with HNSCC. We also performed functional analyses of HPRT1 coexpressed genes and examined the association between HPRT1 expression and drug sensitivity. Both HPRT1 mRNA and protein were significantly higher in HNSCC compared with normal tissues, and up-regulation of HPRT1 was also correlated with age, sex, pathological stage and histological grades of patients with HNSCC. Moreover, HPRT1 and its associated genes were observed to be enriched for several cancer-related pathways, including DNA replication and cell cycle. Finally, patients exhibiting overexpression of the HPRT1 gene may be resistant to abiraterone and sensitive to several drugs, including tozasertib and teniposide. This study demonstrated that the elevated expression of HPRT1 gene is correlated with the progression of HNSCC; thus, this gene may serve as a useful indicator for the early detection, risk stratification and targeted therapy of patients with HNSCC.
