MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.
MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.
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DOI：
10.1371/journal.pone.0108483
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Maizels N
中科院分区：
文献类型：
--
作者：
Pavelitz T;Renfro L;Foster NR;Caracol A;Welsch P;Lao VV;Grady WB;Niedzwiecki D;Saltz LB;Bertagnolli MM;Goldberg RM;Rabinovitch PS;Emond M;Monnat RJ Jr;Maizels N
错配修复缺陷（MMR）的结肠癌可能表现出DNA修复基因MRE 11表达减少，这是T11单核苷酸链收缩的结果。本研究调查了III期结肠癌患者的MRE 11状态及其与预后、生存率和药物反应的关系。癌症和白血病组B 89803（Alliance）将1,264例III期结肠癌患者随机分配至术后每周辅助推注5-氟尿嘧啶/亚叶酸（FU/LV）或伊立替康+FU/LV（IFL），随访8年。对这些患者的肿瘤进行分析，以确定MRE 11基因中T11段的稳定性。主要终点是总生存期（OS），次要终点是无病生存期（DFS）。在考克斯分析中使用时间依赖性协变量解决非比例风险。在检查的625例肿瘤病例中，70例（11.2%）在一个或两个MRE 11等位基因中表现出T11束收缩，因此预测为MRE 11（dMRE 11）缺陷。在汇总治疗分析中，与MRE 11 T11束完整的患者相比，dMRE 11患者显示初始DFS和OS降低，但长期DFS和OS改善。在接受IFL治疗的dMRE 11患者亚组中，观察到不明原因的早期死亡率增加，但长期DFS优于接受IFL治疗的pMRE 11患者。对这一相对少量的患者和事件的分析表明，dMRE 11标志物预测长期独立于治疗的更好预后。在亚组分析中，接受伊立替康治疗的dMRE 11患者出现无法解释的短期死亡。MRE 11状态易于检测，因此可能被证明是一个有用的预后标志物，前提是本文报告的相对少数患者的结果可以在大量样本的独立分析中推广。ClinicalTrials.gov NCT00003835
Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. ClinicalTrials.gov NCT00003835
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影响因子：
4.5
作者：
Gómez-Herreros F;Romero-Granados R;Zeng Z;Alvarez-Quilón A;Quintero C;Ju L;Umans L;Vermeire L;Huylebroeck D;Caldecott KW;Cortés-Ledesma F
通讯作者：
Cortés-Ledesma F
DOI：
10.1016/s1383-5742(00)00058-2
发表时间：
2001-03-01
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5.3
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通讯作者：
Peltomäki, P
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影响因子：
45.3
作者：
Saltz, Leonard B.;Niedzwiecki, Donna;Mayer, Robert J.
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影响因子：
10.3
作者：
Sinicrope, Frank A.;Foster, Nathan R.;Sargent, Daniel J.
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Sargent, Daniel J.