MRE11 and ATM Expression Levels Predict Rectal Cancer Survival and Their Association with Radiotherapy Response.
MRE11 and ATM Expression Levels Predict Rectal Cancer Survival and Their Association with Radiotherapy Response.
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DOI：
10.1371/journal.pone.0167675
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Shin JS
中科院分区：
文献类型：
--
作者：
Ho V;Chung L;Revoltar M;Lim SH;Tut TG;Abubakar A;Henderson CJ;Chua W;Ng W;Lee M;De Souza P;Morgan M;Lee CS;Shin JS
DNA修复蛋白的异常表达与癌症患者的生存率低有关。我们研究了MRE11和ATM的联合表达作为直肠癌放疗反应的预测标志物。在来自262名接受直肠癌手术的直肠癌患者的肿瘤样本中检查了MRE 11和ATM表达，其中包括54名接受新辅助放疗的患者的子队列。通过Mann-Whitney U检验和受试者工作特征曲线下面积（ROC-AUC）分析评估两种蛋白质组的表达与肿瘤消退等级（TRG）之间的关系。Kaplan-Meier法和考克斯回归分析检测两种蛋白的表达与临床病理变量和生存率之间的关系。肿瘤中心（TC）的两种蛋白联合表达的高评分与整个队列中较差的无病生存期（DFS）（P = 0.035）和总生存期（OS）（P = 0.003）显著相关，与新辅助亚组（n = 54）中的DFS（P = 0.028）和OS（P = 0.024）显著相关。多因素分析显示，两种蛋白组合（HR = 2.178，95%CI 1.115 - 4.256，P = 0.023）和神经周围浸润（HR = 2.183，95%CI 1.222 - 3.899，P = 0.008）与DFS显著相关。在术前接受放疗的患者中，使用ROC-AUC分析组织学肿瘤缓解良好与不良，合并组的平均ROC-AUC为0.745，ATM单独组为0.618，MRE 11单独组为0.711。本研究开发的MRE 11/ATM双蛋白组可能具有临床价值，可作为肿瘤对新辅助放疗反应的预测标志物，以及无病生存和总生存的预后标志物。
Aberrant expression of DNA repair proteins is associated with poor survival in cancer patients. We investigated the combined expression of MRE11 and ATM as a predictive marker of response to radiotherapy in rectal cancer. MRE11 and ATM expression were examined in tumor samples from 262 rectal cancer patients who underwent surgery for rectal cancer, including a sub-cohort of 54 patients who were treated with neoadjuvant radiotherapy. The relationship between expression of the two-protein panel and tumor regression grade (TRG) was assessed by Mann–Whitney U test and receiver operating characteristics area under curve (ROC-AUC) analysis. The association between expression of the two-protein panel and clinicopathologic variables and survival was examined by Kaplan-Meier methods and Cox regression analysis. A high score for two-protein combined expression in the tumor center (TC) was significantly associated with worse disease-free survival (DFS) (P = 0.035) and overall survival (OS) (P = 0.003) in the whole cohort, and with DFS (P = 0.028) and OS (P = 0.024) in the neoadjuvant subgroup (n = 54). In multivariate analysis, the two-protein combination panel (HR = 2.178, 95% CI 1.115–4.256, P = 0.023) and perineural invasion (HR = 2.183, 95% CI 1.222–3.899, P = 0.008) were significantly associated with DFS. Using ROC-AUC analysis of good versus poor histological tumor response among patients treated preoperatively with radiotherapy, the average ROC-AUC was 0.745 for the combined panel, 0.618 for ATM alone, and 0.711 for MRE11 alone. The MRE11/ATM two-protein panel developed in this study may have clinical value as a predictive marker of tumor response to neoadjuvant radiotherapy, and a prognostic marker for disease-free and overall survival.
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3.7
作者：
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