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增殖细胞核抗原(PCNA)表达在骨肉瘤患者中的预后价值:一项对16项研究的荟萃分析。

The prognostic value of PCNA expression in patients with osteosarcoma: A meta-analysis of 16 studies.

作者信息

Wang Xing, Wang Dong, Yuan Na, Liu Fanxiao, Wang Fu, Wang Bomin, Zhou Dongsheng

机构信息

Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan Department of Orthopedic Surgery, Laiwu Hospital Affiliated to Taishan Medical College, Laiwu Department of Orthopedics, Zoucheng People's Hospital, Zoucheng Department of Orthopedics, Yankuang Group General Hospital, Zoucheng, Shandong, China Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University of Munich (LMU), Munich, Germany.

出版信息

Medicine (Baltimore). 2017 Oct;96(41):e8254. doi: 10.1097/MD.0000000000008254.

Abstract

BACKGROUND

Numerous studies have attempted to determine the prognostic role of proliferating cell nuclear antigen (PCNA) expression in patients with osteosarcoma with no consistent conclusion. We performed this meta-analysis to systematically elucidate the association in a more precise manner.The purpose of this meta-analysis is to determine the prognostic role of PCNA in patients with osteosarcoma.

METHODS

A systematic search of relevant studies was performed in 6 electronic databases including PubMed, Embase, Web of Science, Wanfang database, China National Knowledge Internet (CNKI) database, and Chinese Biological Medical (CBM) Database (up to March 1, 2016) with the following keywords: (PCNA OR proliferating cell nuclear antigen) AND (osteosarcoma OR osteogenic tumor). A manual search of references on relevant articles was also conducted by 2 investigators independently. We performed a comprehensive evaluation of the correlation between PCNA expression and overall survival (OS) or disease-free survival (DFS) by calculating relative ratios (RR) and their corresponding 95% confidence intervals (CI) using STATA software. A fixed- or random-effect model was chosen based on the between-study heterogeneity.

RESULTS

In total, 16 studies with 691 osteosarcoma patients were included in this meta-analysis. PCNA overexpression was found in approximately 57.31% of the patients with osteosarcoma. The meta-analysis suggested that PCNA overexpression in osteosarcoma patients is associated with low OS, but not significantly with DFS (RR = 1.82, 95% CI 1.53-2.18, P = .000; RR = 1.15, 95% CI 0.91-1.44, P = 0.234). Sensitivity analysis for OS and DFS showed no significant difference and the pooled RRs were stable when the included studies were removed one by one. Similar results were also obtained for subgroup analysis based on different follow-ups and cutoffs to determine PCNA expression.

CONCLUSION

The findings from this meta-analysis indicate that PCNA overexpression is an effective biomarker for poor prognosis in patients with osteosarcoma for OS. Hence, more large-scale studies are still needed to further warrant this conclusion.

摘要

背景

众多研究试图确定增殖细胞核抗原(PCNA)表达在骨肉瘤患者中的预后作用,但结论并不一致。我们进行这项荟萃分析以更精确地系统阐明这种关联。本荟萃分析的目的是确定PCNA在骨肉瘤患者中的预后作用。

方法

在包括PubMed、Embase、Web of Science、万方数据库、中国知网(CNKI)数据库和中国生物医学文献数据库(CBM)数据库(截至2016年3月1日)在内的6个电子数据库中,使用以下关键词进行相关研究的系统检索:(PCNA或增殖细胞核抗原)和(骨肉瘤或成骨性肿瘤)。2名研究人员还独立对相关文章的参考文献进行了手工检索。我们使用STATA软件通过计算相对比率(RR)及其相应的95%置信区间(CI),对PCNA表达与总生存期(OS)或无病生存期(DFS)之间的相关性进行了综合评估。根据研究间的异质性选择固定效应或随机效应模型。

结果

本荟萃分析共纳入16项研究,涉及691例骨肉瘤患者。在大约57.31%的骨肉瘤患者中发现PCNA过表达。荟萃分析表明,骨肉瘤患者中PCNA过表达与低OS相关,但与DFS无显著相关性(RR = 1.82,95% CI 1.53 - 2.18,P = 0.000;RR = 1.15,95% CI 0.91 - 1.44,P = 0.234)。OS和DFS的敏感性分析显示无显著差异,当逐一剔除纳入的研究时,合并的RR值稳定。基于不同随访和确定PCNA表达的临界值进行亚组分析也得到了类似结果。

结论

本荟萃分析的结果表明,PCNA过表达是骨肉瘤患者OS预后不良的有效生物标志物。因此,仍需要更多大规模研究来进一步证实这一结论。

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