Clinical Significance Of Clock Gene PER2 Expression In Human Oral Squamous Cell Carcinoma And Its Correlation With Important Tumor-related Genes

Background:Recent studies have demonstrated that abnormal expression of the clock gene PER2 is closely associated with the development of a variety of cancer types.However,the expression of PER2 in oral squamous cell carcinoma(OSCC),a common malignant tumor in humans,and its correlations with the clinicopathological parameters and survival time of OSCC patients and the altered expression of important tumor-related genes remain unclear.Objective:explore the expression of clock gene PER2 in OSCC and its clinical significance and correlations with tumor related genes PER2,PIK3CA,PTEN,P53,P14ARF and caspase-8.Methods:mRNA and protein expression levels of PER2,PIK3CA,PTEN,P53,P14ARF and caspase-8 in OSCC tissues and cancer-adjacent oral mucosa were detected by reverse transcription-quantitative PCR(RT-qPCR),western blotting and immunohistochemistry.Correlation between PER2 expression and clinical parameters of OSCC patients was analyzed by x 2 test.Correlation between PER2 expression and important tumor related genes,such as PIK3CA,PTEN,P53,P14ARF and caspase-8,were analyzed by Spearman's rank correlation.Survival curves were drawn using the Kaplan-Meier method,and log-rank was used to compare survival between PER2-positive and PER2-negative cases.Results:PER2,PTEN,P53,P14ARF and caspase-8 mRNA and protein expression levels in OSCC were significantly reduced compared with those in cancer-adjacent tissues.Additionally,the PIK3CA protein expression level was significantly increased in OSCC tissues,whereas the mRNA level was not.Decreased expression of PER2 was significantly associated with advanced clinical stage and the presence of lymphatic metastasis in OSCC patients.Patients with PER2-negative expression had a significantly shorter survival time than those with PER2-positive expression.PER2 expression was negatively correlated with PIK3CA and P53 levels,and positively correlated with PTEN,P14ARF and caspase-8 levels.Conclusion:Loss of PER2 expression is closely associated with the genesis and development of OSCC and that PER2 may be an important prognostic biomarker in OSCC.PER2 may serve an antitumor role via the P53/P14ARF,PIK3CA/AKT and caspase-8 pathways.