Student Research Committee, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
FEBS Open Bio. 2021 Sep;11(9):2525-2540. doi: 10.1002/2211-5463.13250. Epub 2021 Aug 4.
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.
次黄嘌呤磷酸核糖转移酶 1(HPRT1)作为一种补救途径酶,在调节细胞周期中起着至关重要的作用,并且已被报道在多种癌症中过度表达。然而,HPRT1 基因与头颈部鳞状细胞癌(HNSCC)之间的关系迄今尚未得到研究。在这项研究中,我们首先评估了 HPRT1 mRNA 和蛋白质在肿瘤和健康对照组织中的表达和临床价值。然后,我们检查了 HPRT1 基因的突变及其与 HNSCC 患者生存结局的关系。我们还进行了 HPRT1 共表达基因的功能分析,并检查了 HPRT1 表达与药物敏感性之间的关联。HNSCC 中的 HPRT1 mRNA 和蛋白质水平均明显高于正常组织,并且 HPRT1 的上调也与 HNSCC 患者的年龄、性别、病理分期和组织学分级相关。此外,还观察到 HPRT1 及其相关基因与几种癌症相关途径富集,包括 DNA 复制和细胞周期。最后,表现出 HPRT1 基因过表达的患者可能对阿比特龙耐药,对几种药物敏感,包括托扎替布和替尼泊苷。这项研究表明,HPRT1 基因的高表达与 HNSCC 的进展相关;因此,该基因可能作为 HNSCC 患者早期检测、风险分层和靶向治疗的有用指标。