Abnormal Transcription And Expression Of HPRT1 In Head And Neck Squamous Cell Carcinoma

Background:Head and Neck Squamous Cell Carcinoma(HNSCC)is the sixth most common malignancy in the world.HNSCC is related to smoking,drinking,and human papillomavirus(HPV)infection.HNSCC is concealed that most patients are in advanced stage at the time of the first visit.Although the treatments based on surgery,radiation therapy and simple systemic therapy are developing,the survival rate of patients is still low.Effective biomarkers that can evaluate the prognostic values of HNSCC was urgently needed.At present,more and more studies have shown that purine metabolism abnormalities are closely related to tumors,hypoxanthine guanine phosphoribosyl transferase(HPRT1)plays an essential role in the purine salvage pathway.The expression of purine salvage pathway key genes HPRT1,molecular mechanisms and translational medical significance in HNSCC have not yet been elucidated.Objective:Through the integration of bioinformatics analysis,molecular biology and the validation of clinical samples,to explore the transcription and expression levels of HPRT1 in HNSCC and elucidate the relationship with the clinicopathological features of patients.To explore the mechanism of HPRT1 in HNSCC and new strategies for finding new tumor markers and therapeutic targets.Methods:1.We analyzed the abnormal transcription of HPRT1 in Various types of tumors including Head and Neck Squamous Cell Carcinoma from the Oncomine database.2.We analyzed the association between abnormal transcription of HPRT1 and clinicopathological parameters in HNSCC patients from the TCGA database.3.The protein expression of HPRT1 in Head and Neck Squamous Cell Carcinoma and normal control tissues were detected by immunohistochemical staining.4.We analyzed the association between abnormal transcription of HPRT1 and survival prognosis in HNSCC patients by K-M plotter database.5.We analyzed the association between transcription level of HPRT1 and survival prognosis in HNSCC patients by GEPIA.6.We analyzed mutation of HPRT1 in HNSCC by COSMIC and cBioPortal tools.7.We use KEGG-Pathway analysis to find possible functions and pathways affected by HPRT1 gene.8.We use Transwell cell invasion experiment in vitro to observe the invasion and migration of tumor cells,study the relationship between HPRT1 and the ability of tumor cells to clone and grow by operating clone formation experiment.Results:1.Abnormal transcription of HPRT1 found in various types of cancer.In Oncomine database,it was found HPRT1 transcription upregulation in various types of human cancer.2.The transcription of HPRT1 gene was up-regulated in HNSCC.Through the integration of Oncomine database,UALCAN tools associated with TCGA database,it was found that the transcription of HPRT1 was upregulated in HNSCC.3.The expression of HPRT1 was up-regulated in HNSCC.Through the immunohistochemistry analysis,it was found that the expression of HPRT1 was up-regulated in HNSCC.4.The transcription of HPRT1 gene was related to high T stage and lymph node metastasis.By analyzing the relationship between HPRT1 transcription and clinicopathological features in TCGA-HNSCC patients,it suggested that the high transcription of HPRT1 gene was associated with high T stage and lymph node metastasis.Head and neck tumor Immunohistochemistry results were not found to be associated with clinicopathological features of HNSCC patients.5.High transcription of HPRT1 gene was related to poor survival prognosis in patients with HNSCC.The KM-plotter database and GEPIA(Gene Expression Profiling Interactive Analysis)suggested that abnormally high transcription of the HPRT1 gene was related to low OS and DFS in HNSCC patients.6.The mutation of the HPRT1 gene has low ratio and has relate without prognosis in HNSCC patients.The mutation of HPRT1 in HNSCC was further studied by COSMIC and cBioPortal,it suggested that the mutation of the HPRT1 gene has low ratio.KM plotter suggested that the mutation of the HPRT1 gene was not related to OS and DFS in HNSCC patients.7.HPRT1 gene is mainly involved in purine metabolism,drug metabolism-other enzymes and hypoxanthine phosphoribosyl transferase and other processesThrough KEGG pathway enrichment analysis,it was found that HPRT1 is mainly involved in purine metabolism,drug metabolism-other enzymes and hypoxanthine phosphoribosyl transferase.8.Knockdown of HPRT1 gene inhibited the invasive ability of laryngeal cancer cells,but does not affect cell migration and proliferation.After the construction of the knockdown HPRT1 cell line and control cell line,through the Transwell in vitro cell invasion experiment,it was found that knocking down the HPRT1 gene reduced the invasion ability of the throat cancer cells.Scratch and proliferation experiments found that knocking down the HPRT1 gene did not change the migration and proliferation ability of laryngeal cancer cells.Conclusions:1.The transcription and expression of HPRT1 was up-regulated in HNSCC2.The high transcription of HPRT1 gene was associated with high T stage,lymph node metastasis and poor prognosis in HNSCC.3.The HPRT1 gene has low frequency mutations in HNSCC,but genetic mutations may not be the main reason for the abnormal transcription and expression of the HPRT1 gene in HNSCC.4.HPRT1 gene enhances the invasion ability of laryngeal cancer cells.In summary,the purine salvage pathway key genes HPRT1 was abnormally transcript and expressed in HNSCC,and affected the clinical stage and prognosis of the patients,HPRT1 gene enhances the invasion ability of laryngeal cancer cells.These results suggested that HPRT1 may play an important role in the pathogenesis of HNSCC and may be tumor marker for HNSCC diagnosis and prognosis.