Campone Mario, Valo Isabelle, Jézéquel Pascal, Moreau Marie, Boissard Alice, Campion Loic, Loussouarn Delphine, Verriele Véronique, Coqueret Olivier, Guette Catherine
‡René Gauducheau ICO Cancer Center, Inserm U892, CNRS 6299, Bd J. Monod, 44805 Saint Herblain Cedex, France; §Paul Papin ICO Cancer Center, Inserm U892, CNRS 6299, 2 rue Moll, 49933 Angers Cedex 9, France;
§Paul Papin ICO Cancer Center, Inserm U892, CNRS 6299, 2 rue Moll, 49933 Angers Cedex 9, France;
Mol Cell Proteomics. 2015 Nov;14(11):2936-46. doi: 10.1074/mcp.M115.048967. Epub 2015 Jul 24.
To date, there is no available targeted therapy for patients who are diagnosed with triple-negative breast cancers (TNBC). The aim of this study was to identify a new specific target for specific treatments. Frozen primary tumors were collected from 83 adjuvant therapy-naive TNBC patients. These samples were used for global proteome profiling by iTRAQ-OFFGEL-LC-MS/MS approach in two series: a training cohort (n = 42) and a test set (n = 41). Patients who remains free of local or distant metastasis for a minimum of 5 years after surgery were classified in the no-relapse group; the others were in the relapse group. OPLS and Kaplan-Meier analyses were performed to select candidate markers, which were validated by immunohistochemistry. Three proteins were identified in the training set and validated in the test set by Kaplan-Meier method and immunohistochemistry (IHC): TrpRS as a good prognostic markers and DP and TSP1 as bad prognostic markers. We propose the establishment of an IHC test to calculate the score of TrpRS, DP, and TSP1 in TNBC tumors to evaluate the degree of aggressiveness of the tumors. Finally, we propose that DP and TSP1 could provide therapeutic targets for specific treatments.
迄今为止,对于被诊断为三阴性乳腺癌(TNBC)的患者,尚无可用的靶向治疗方法。本研究的目的是确定一种用于特定治疗的新的特异性靶点。从83例未接受过辅助治疗的TNBC患者中收集了冷冻的原发性肿瘤。这些样本通过iTRAQ-OFFGEL-LC-MS/MS方法用于两个系列的全蛋白质组分析:一个训练队列(n = 42)和一个测试集(n = 41)。术后至少5年无局部或远处转移的患者被归类为无复发组;其他患者则为复发组。进行了OPLS和Kaplan-Meier分析以选择候选标志物,并通过免疫组织化学进行验证。在训练集中鉴定出三种蛋白质,并通过Kaplan-Meier方法和免疫组织化学(IHC)在测试集中进行了验证:色氨酸-tRNA合成酶(TrpRS)作为良好的预后标志物,而二氢嘧啶脱氢酶(DP)和血小板反应蛋白1(TSP1)作为不良预后标志物。我们建议建立一种免疫组织化学检测方法,以计算TNBC肿瘤中TrpRS、DP和TSP1的评分,从而评估肿瘤的侵袭程度。最后,我们提出DP和TSP1可为特定治疗提供治疗靶点。