Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data
Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data
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DOI：
10.1016/j.ejca.2010.05.009
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发表时间：
2010-10-01
影响因子：
8.4
通讯作者：
Dogliotti, Eugenia
中科院分区：
文献类型：
--
作者：
Guastadisegni, Cecilia;Colafranceschi, Mauro;Dogliotti, Eugenia
背景和方法：我们回顾并汇总了已发表的研究数据，以评估微卫星不稳定性（MSI）和结直肠癌（CRC）预后之间的关系。31个合格的研究报告生存12782例患者的特点为MSI汇总使用固定或随机效应model.Results：总生存率（OS）与MSI相关的总比值比（OR）估计为0.6（95%CI 0.53-0.69，p < 0.0001），没有异质性的证据。对无病生存期（DFS）的影响相似（OR = 0.58，95%CI 0.47-0.72，p < 0.0001）。在接受5-氟尿嘧啶（5-FU）为基础的化疗的患者亚组中，发现微卫星稳定（MSS）肿瘤的预后显著改善（OR = 0.52，95%CI 0.4-0.6，p < 0.0001），无异质性（p = 0.53; I-2 = 0%）。相比之下，396例MSI肿瘤患者的数据具有较大的异质性（OR = 0.69，95%CI 0.3-1.5，p = 0.1;异质性：p = 0.03; I-2 = 58%）。结论：本研究证实了MSI与CRC患者OS和DFS确定的良好预后之间的相关性。发现5-FU治疗对MSS肿瘤有显著的有益作用，而由于研究间异质性较高，未得出MSI肿瘤的明确结论。我们认为，这种不确定的结果是由于使用了单一的标记，如MSI，不能单独解释5-FU细胞毒性机制的复杂性。未来预测5-FU化疗反应的研究应包括额外的基因组稳定性标志物。(C)2010爱思唯尔有限公司保留所有权利。
Background and methods: We have reviewed and pooled data from published studies to evaluate the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Thirty-one eligible studies reporting survival in 12782 patients characterised for MSI were pooled using a fixed- or random-effects model.Results: The summary odds ratio (OR) estimate for overall survival (OS) associated with MSI was 0.6 (95%CI 0.53-0.69, p < 0.0001), with no evidence of heterogeneity. The effect was similar for disease-free survival (DFS) (OR = 0.58, 95%CI 0.47-0.72, p < 0.0001). In a subset of patients treated with 5-fluorouracil (5-FU)-based chemotherapy a significant improved prognosis was found for microsatellite stable (MSS) tumours (OR = 0.52, 95%CI 0.4-0.6, p < 0.0001) with no heterogeneity (p = 0.53; I-2 = 0%). By contrast a large heterogeneity characterised the data relative to 396 patients with MSI tumours (OR = 0.69, 95%CI 0.3-1.5, p = 0.1; heterogeneity: p = 0.03; I-2 = 58%).Conclusions: This study confirmed the association between MSI and favourable prognosis as determined by both OS and DFS of CRC patients. A significant beneficial effect of 5-FU therapy was found for MSS tumours whilst no clear conclusion was reached for MSI tumours due to the high inter-study heterogeneity. We propose that this inconclusive result is due to the use of a single marker, such as MSI, that cannot account alone for the complexity of the mechanisms underlying 5-FU cytotoxicity. Future studies to predict response to 5-FU chemotherapy should include additional genome stability markers. (C) 2010 Elsevier Ltd. All rights reserved.