Prognostic significance of TP53 tumor suppressor gene expression and mutations in human osteosarcoma:: A meta-analysis
Prognostic significance of TP53 tumor suppressor gene expression and mutations in human osteosarcoma:: A meta-analysis
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DOI：
10.1158/1078-0432.ccr-04-0246
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发表时间：
2004-09-15
影响因子：
11.5
通讯作者：
Ioannidis, JPA
中科院分区：
文献类型：
--
作者：
Pakos, EE;Kyzas, PA;Ioannidis, JPA
目的：各种研究探讨肿瘤抑制蛋白TP 53过表达和/或TP 53基因突变与骨肉瘤患者化疗反应和临床结局之间的关系，但结果不确定。本研究的目的是评估TP 53状态与化疗反应和/或骨肉瘤临床结局的关系。实验设计：我们对16项研究（n = 499例患者）进行了荟萃分析，评估了TP 53状态与化疗组织学反应和2年生存率之间的相关性。数据进行了综合总结受试者工作特征曲线和总结似然比（LRs）和riskriskratios.Results：定量合成显示，TP 53状态是不是一个预后因素的化疗反应。阳性LR为1.21（95%置信区间，0.86-1.71），阴性LR为0.91（95%置信区间，0.77-1.07）。研究间无显著异质性。TP 53阳性状态往往与较差的2年生存率相关，但总体结果没有正式的统计学意义。在明确说明测量结果不受影响的研究中，这种关联在形式上是显著的（风险比，2.05; 95%置信区间，1.23-3.44），以及使用逆转录-PCR评价TP 53改变的研究（风险比，1.76; 95%可信区间，1.07-2.91）。TP 53状态与骨肉瘤患者化疗的组织学反应无关，而TP 53基因改变可能与存活率降低有关。
Purpose: Various studies examining the relationship between tumor suppressor protein TP53 overexpression and/or TP53 gene mutations and the response to chemotherapy and clinical outcome in patients with osteosarcoma have yielded inconclusive results. The purpose of the current study was to evaluate the relation of TP53 status with respouse to chemotherapy and/or clinical outcome in osteosarcoma.Experimental Design: We conducted a meta-analysis of 16 studies (n = 499 patients) that evaluated the correlation between TP53 status and histologic response to chemotherapy and 2-year survival. Data were synthesized in summary receiver operating characteristic curves and with summary likelihood ratios (LRs) and risk ratios.Results: The quantitative synthesis showed that TP53 status is not a prognostic factor for the response to chemotherapy. The positive LR was 1.21 (95% confidence interval, 0.86-1.71), and the negative LR was 0.91 (95% confidence interval, 0.77-1.07). There was no significant between-study heterogeneity. TP53-positive status tended to be associated with a worse 2-year survival, but the overall results were not formally statistically significant. The association was formally significant in studies that clearly stated that measurements were blinded to outcomes (risk ratio, 2.05; 95% confidence interval, 1.23-3.44), and in studies using reverse transcription-PCR for evaluating TP53 alterations (risk ratio, 1.76; 95% confidence interval, 1.07-2.91).Conclusions: TP53 status is not associated with the histologic response to chemotherapy in patients with osteosarcoma, whereas TP53 gene alterations may be associated with decreased survival.