Gámez-Pozo Angelo, Trilla-Fuertes Lucía, Prado-Vázquez Guillermo, Chiva Cristina, López-Vacas Rocío, Nanni Paolo, Berges-Soria Julia, Grossmann Jonas, Díaz-Almirón Mariana, Ciruelos Eva, Sabidó Eduard, Espinosa Enrique, Fresno Vara Juan Ángel
Molecular Oncology & Pathology Lab, Instituto de Genética Médica y Molecular-INGEMM, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
Biomedica Molecular Medicine SL, Madrid, Spain.
PLoS One. 2017 Jun 8;12(6):e0178296. doi: 10.1371/journal.pone.0178296. eCollection 2017.
Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and usually requires the administration of adjuvant chemotherapy after surgery but even with this treatment many patients still suffer from a relapse. The main objective of this study was to identify proteomics-based biomarkers that predict the response to standard adjuvant chemotherapy, so that patients at are not going to benefit from it can be offered therapeutic alternatives.
We analyzed the proteome of a retrospective series of formalin-fixed, paraffin-embedded TNBC tissue applying high-throughput label-free quantitative proteomics. We identified several protein signatures with predictive value, which were validated with quantitative targeted proteomics in an independent cohort of patients and further evaluated in publicly available transcriptomics data.
Using univariate Cox analysis, a panel of 18 proteins was significantly associated with distant metastasis-free survival of patients (p<0.01). A reduced 5-protein profile with prognostic value was identified and its prediction performance was assessed in an independent targeted proteomics experiment and a publicly available transcriptomics dataset. Predictor P5 including peptides from proteins RAC2, RAB6A, BIEA and IPYR was the best performance protein combination in predicting relapse after adjuvant chemotherapy in TNBC patients.
This study identified a protein combination signature that complements histopathological prognostic factors in TNBC treated with adjuvant chemotherapy. The protein signature can be used in paraffin-embedded samples, and after a prospective validation in independent series, it could be used as predictive clinical test in order to recommend participation in clinical trials or a more exhaustive follow-up.
三阴性乳腺癌（TNBC）占所有乳腺癌的15%-20%，通常术后需要进行辅助化疗，但即便接受这种治疗，许多患者仍会复发。本研究的主要目的是识别基于蛋白质组学的生物标志物，以预测对标准辅助化疗的反应，从而为那些无法从该治疗中获益的患者提供治疗选择。
我们采用高通量无标记定量蛋白质组学分析了一系列福尔马林固定、石蜡包埋的TNBC组织的蛋白质组。我们识别出了几种具有预测价值的蛋白质特征，并在独立的患者队列中通过定量靶向蛋白质组学进行了验证，还在公开的转录组学数据中进行了进一步评估。
通过单变量Cox分析，一组18种蛋白质与患者的无远处转移生存期显著相关（p<0.01）。我们识别出了一个具有预后价值的简化的5蛋白特征，并在独立的靶向蛋白质组学实验和公开的转录组学数据集中评估了其预测性能。预测因子P5包括来自RAC2、RAB6A、BIEA和IPYR蛋白的肽段，是预测TNBC患者辅助化疗后复发的最佳性能蛋白质组合。
本研究识别出了一种蛋白质组合特征，可补充辅助化疗治疗的TNBC中的组织病理学预后因素。该蛋白质特征可用于石蜡包埋样本，在独立系列中进行前瞻性验证后，可作为预测性临床检测，以推荐参与临床试验或进行更全面的随访。
