Period Family Of Clock Genes As Novel Predictors Of Survival In Human Cancer:a Systematic Review And Meta-analysis

Purpose: Period genes includes PER1,PER2 and PER3,which are the core circadian clock genes.A number of studies have demonstrated that the abnormal expression of the PER gene family of clock genes is associated with the survival and prognosis of patients with cancer;however,the sample sizes included in the majority of these studies were small,and the results reported were discrepant.This study was the first to collect the relevant publications to systematically evaluate the value of the expression of PER gene family in the prediction of survival and prognosis of human tumors.Methods: The PubMed,Cochrane library,Embase and Web of Science databases were searched systematically.Experimental studies that focused on the association between the expression of the PER gene family of clock genes and the prognosis of human cancer were screened.The quality of the included literatures in the study were evaluated using the NewCastle Ottawa scale.A meta-analysis was performed to quantitatively synthesize the experimental results,and the associations between theexpression of the PER gene family(PER1-3)proteins,mRNA and the prognosis of cancer was evaluated.In addition,sensitivity analyses and publication bias evaluations were performed.Results: A total of 12 eligible publications met the inclusion criteria for the meta-analysis,including 1,369 patients and 9 different types of cancer.The pooled hazard ratio(HR)for overall survival indicated that the overall survival of patients in the high PER1 protein expression group [HR,0.67;95% confidence interval(CI),0.52-0.88;p=0.003],high PER2 protein expression group(HR,0.55;95% CI,0.42-0.71;p=0.000)and high PER3 protein expression group(HR,0.47;95% CI,0.33-0.66;p=0.000)was significantly higher than that in the low expression group.The sensitivity analysis revealed that the result was stable and reliable.The association between PER1 and PER3 mRNA expression levels and cancer prognosis was not meta-analyzed as the number of experimental studies was <3.There was no significant association between the expression of PER2 mRNA and the overall survival of patients with cancer(HR,0.92;95% CI,0.80-1.06;p=0.247).No publication bias was detected when using a funnel plot or Begg's test on the aforementioned results.Conclusion: PER1,PER2 and PER3 protein expression levels can be used as novel potential biomarkers for predicting cancer prognosis.