| Objective:Many factors cause the activation of the tumour suppressor wild-type P53 gene and further modulate the amplification and expression of the P21WAF1/CIP1 gene.The complex of cyclin and cyclin-dependent kinase can combine with P21 protein and lose its own activation,thereby arresting the cell cycle in G1 phase without entering S phase.Many previous studies have shown that the expression levels of the P21WAF1/CIP1 gene and the product P21 protein correlate with survival and prognosis in breast cancer patients,but different studies have produced discrepant results.The results of the Meta-analysis of the P21WAF1/CIP1 gene and P21 protein expression levels in correlation with the prognosis of breast cancer patients have not been published nationally or internationally.This study collected all data from relevant studies published so far and performed Meta-analysis,aiming to evaluate the value of P21WAF1/CIP1 gene and product P21 protein in the judgment of survival and prognosis of breast cancer patients,and to provide evidence-based evidence for the assessment of breast cancer prognosis.Methods:Boolean logical operators(AND,OR,NOT)were used to search the English databases such as EMBASE database,Pub Med database,Web of Science database,Cochrane Library database and Chinese databases such as China Academic Journals(Wanfang Data)database,China Knowledge Network database(CNKI)and Chinese Science and Technology Journals(Wipu.com)database by subject terms combined with free terms.All literature published between January 1993 and August 2022 assessing the relationship between P21WAF1/CIP1 gene and product P21 protein expression levels and survival and prognosis of breast cancer patients were searched in the above databases,and all literature was subsequently screened according to the exclusion criteria developed by the investigators.In terms of quality evaluation,since all the original studies were observational cohort study,the researchers chose the Newcastle Ottawa Scale(NOS)scoring method to evaluate the quality of the included literature.Numerous Meta-analysis steps such as heterogeneity test,subgroup analysis,sensitivity analysis,effect size combination and bias test were performed in Review Manager version 5.4.1 software to evaluate the value of P21WAF1/CIP1 gene expression and product P21 protein in determining survival and prognosis of breast cancer patients.Results:In this study,747 publications were searched through the database and 2 were searched manually.After going through screening of the literature and quality evaluation of the literature,18 papers were finally included,and the total sample size of the 18 papers was 3246 tissue specimens from breast cancer patients.The final results of the Meta-analysis of this study suggested that patients in the group with high expression of the P21WAF1/CIP1 gene(P21 protein positive)showed a significant shortening of OS compared to the group with low expression(P21 protein negative)(HR=2.69,95% CI: 1.89-3.82,P＜0.00001),and patients in the group with high expression of P21WAF1/CIP1 gene(P21 protein positive)showed a significant shortening of DFS(RFS)compared with the group with low expression(P21 protein negative)(HR=1.80,95% CI: 1.44-2.26,P＜0.00001),and all these results were statistically significant.In addition,there is also a literature implicated that high expression of the P21WAF1/CIP1 gene is associated with shorter disease-specific survival(DSS)in breast cancer patients(RR=1.54,95% CI: 1.02-2.32,P=0.0419).Because there was only 1 study related to DSS,Meta-analysis of relevant data was not performed.The results of the funnel plot indicated that publication bias was not statistically significant.Conclusions:The final results of this Meta-analysis showed that breast cancer patients with high expression of the P21WAF1/CIP1 gene and its product P21 protein positive were associated with short survival and that the P21WAF1/CIP1 gene and P21 protein could be used as indicators for the assessment of survival and prognosis of breast cancer patients. |
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