microRNA-Associated Progression Pathways and Potential Therapeutic Targets Identified by Integrated mRNA and microRNA Expression Profiling in Breast Cancer
microRNA-Associated Progression Pathways and Potential Therapeutic Targets Identified by Integrated mRNA and microRNA Expression Profiling in Breast Cancer
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DOI：
10.1158/0008-5472.can-11-0489
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发表时间：
2011-09-01
期刊：
影响因子：
11.2
通讯作者：
Ragoussis, Jiannis
中科院分区：
文献类型：
--
作者：
Buffa, Francesca M.;Camps, Carme;Ragoussis, Jiannis
microRNA表达谱在癌症分类和治疗策略的鉴定中起着新兴的作用。在这项研究中，我们评估了microRNA-mRNA联合分析在乳腺癌中的益处。匹配的mRNA和microRNA全球表达谱在一个有完整10年随访的207例病例的注释队列中进行。包括microRNA表达、mRNA表达和临床协变量的惩罚性考克斯回归用于鉴定与无远处复发生存期（DRFS）相关的microRNA，其提供独立的预后信息，并且不是先前鉴定的预后协变量的简单替代物。选择惩罚回归以防止过拟合。此外，microRNA-mRNA关系通过全局表达分析进行了探索，并用于验证几个已发表队列的结果（n = 592例DRFS，n = 1，050例无复发生存）。（3例新的和1例已知的; miR-128 a）和6例ER阴性（5例新的和1例已知的; miR-210）病例。在后者中，miR-342、-27 b和-150在三重受体阴性肿瘤中也是预后性的。预测的靶基因和预后microRNA的协调表达加强了这些结果，最显著的是miR-210，-128 a和-27 b，其靶点在几个队列的荟萃分析中具有预后性。此外，miR-210和-128a与它们的同源pri-microRNAs显示出协调的表达，这些pri-microRNAs本身在独立的cohols.Our整合的microRNA-mRNA全局分析方法已经鉴定出与乳腺癌预后独立相关的microRNAs。此外，它还验证了已知和预测的microRNA-靶标相互作用，并阐明了它们与可能代表新型治疗靶标的关键途径的关联。Cancer Res; 71（17）; 5635-45.（C）2011年《非洲标准化评论》。
microRNA expression profiling plays an emerging role in cancer classification and identification of therapeutic strategies. In this study, we have evaluated the benefits of a joint microRNA-mRNA analysis in breast cancer.Matched mRNA and microRNA global expression profiling was conducted in a well-annotated cohort of 207 cases with complete 10-year follow-up. Penalized Cox regression including microRNA expression, mRNA expression, and clinical covariates was used to identify microRNAs associated with distant relapse-free survival (DRFS) that provide independent prognostic information, and are not simply surrogates of previously identified prognostic covariates. Penalized regression was chosen to prevent overfitting. Furthermore, microRNA-mRNA relationships were explored by global expression analysis, and exploited to validate results in several published cohorts (n = 592 with DRFS, n = 1,050 with recurrence-free survival).Four microRNAs were independently associated with DRFS in estrogen receptor (ER)-positive (3 novel and 1 known; miR-128a) and 6 in ER-negative (5 novel and 1 known; miR-210) cases. Of the latter, miR-342, -27b, and -150 were prognostic also in triple receptor-negative tumors. Coordinated expression of predicted target genes and prognostic microRNAs strengthened these results, most significantly for miR-210, -128a, and -27b, whose targets were prognostic in meta-analysis of several cohorts. In addition, miR-210 and -128a showed coordinated expression with their cognate pri-microRNAs, which were themselves prognostic in independent cohorts.Our integrated microRNA-mRNA global profiling approach has identified microRNAs independently associated with prognosis in breast cancer. Furthermore, it has validated known and predicted microRNA-target interactions, and elucidated their association with key pathways that could represent novel therapeutic targets. Cancer Res; 71(17); 5635-45. (C)2011 AACR.