Prognostic Role Of Survivin In Renal Cell Carcinoma:A System Review And Meta-analysis

Objective To make a comprehensive qualitative and quantitative analysis of previous studies,we used the systematic review and meta-analysis method,evaluating the influence of survivin expression on prognosis of renal cell carcinoma patients.Methods According to the purpose of the study,the appropriate inclusion of the necessary references was made based on the research object,research type,expression of survivin and prognosis justification.All relevant literature was collected from the Pub Med,Web of science and Cochrane databases before November 10,2015.The literature languages were restricted to English and Chinese.We selected the literature through the selection of clinical research and the inclusion of standard procedures,and then applied the revised American Society of Clinical Oncology Level of Evidence scale to evaluate the quality of the literature.Electronic documents were used to extract data from the literature.We used Stata(version12)software to perform statistical analysis.The HR and 95% confidence interval were the statistics of merge analysis.The random effect model was used for meta-analysis.We used Begg's and Egger's method to detect publication bias.Result 10 studies satisfied our inclusion criteria,including 1583 renal cell carcinoma patients in total.Three studies were from the United States,three were from China,two were from Germany,one was from Italy and one was from Republic of Korea.CancerSpecific Survival(CSS)was used in seven studies,Overall Survival(OS)was used in two studies,and Recurrence-free Survival(RFS)was used in one study to evaluate the outcomes.Pooling data from two studies showed that high expression of survivin was significantly associated with poor OS in RCC patients(HR = 2.77,95%CI: 1.46-5.26).There was no significant heterogeneity between two studies(P=0.329,I2=0.0%).There were seven studies which reported correlations between survivin expression and CSS.Meta-analysis of these studies showed that survivin over-expression was associated with poor CSS of RCC(HR = 2.85,95% CI: 2.25–3.61),and no significant heterogeneity was found among these studies(P=0.295,I2=17.6%).Only one study evaluated the association between survivin expression and RFS for RCC(HR = 2.92,95%CI: 0.87–7.91).Subgroup analyses were based on the source of survivin(nucleus and cytoplasm or nucleus),sample size(N>100 or ?100),follow up duration(N>5 years or ?5 years),race(Western or Eastern)and detection method(immunostaining or immunohistochemistry).The prognostic value of survivin was consistently significant in each subgroup.Five studies assessed the association between survivin expression from nucleus and cytoplasm and CSS.The combined HRs revealed significant association between high survivin expression and poor CSS in RCC(HR = 2.96,95%CI: 2.33–3.75).Similar result was observed in subgroup where survivin is only from nucleus.We also divided the whole population into two groups according to sample size,and high survivin expression was a significant factor associated with poor CSS in RCC among two subgroups(sample size N>100: HR = 3.09,95%CI: 2.26–4.22;sample size ?100: HR = 2.31,95%CI: 1.51–3.53).Similarly,patients whose followed upduration was less than 5 years or more than 5 years had a nearly significant correlation between high survivin expression and poor CSS in RCC(N>5 years: HR = 3.31,95%CI: 2.01–5.45;?5 years: HR = 2.59,95%CI: 2.00–3.34).In addition,meta-analysis revealed that survivin over-expression was significantly associated with shorter CSS in western patients with RCC(HR = 2.89,95%CI: 2.18–3.83).Meanwhile,grouped according to the detection method,there was no significant heterogeneity among six studies in the immunohistochemistry subgroup(HR= 3.00,95% CI: 2.33–3.85).One study detected by immunostaining method found that survivin expression could be a prognostic factor for the renal cell carcinoma patients.Conclusion In conclusion,our meta-analysis showed that high survivin expression was associated with poor prognosis in patients with renal cell carcinoma.High expression of survivin was significantly associated with poor OS and CSS in RCC patients.Our study found that survivin could be a biological marker of prognosis for the renal cell carcinoma patients.