Cancer Biology Proteomics Group, Postgraduate Medical Institute of the University of Hull, Hull, UK.
J Proteomics. 2012 May 17;75(9):2745-52. doi: 10.1016/j.jprot.2012.03.049. Epub 2012 Apr 3.
Neoadjuvant chemotherapy is used to treat oestrogen receptor-positive breast cancer however chemo-resistance is a major obstacle in this molecular subtype. The ability to predict tumour response would allow chemotherapy administration to be directed towards patients who would most benefit, thus maximising treatment efficacy. We aimed to identify protein biomarkers associated with response to neoadjuvant chemotherapy, in a pilot study using comparative 2-DE MALDI TOF/TOF MS proteomic analysis of breast tumour samples. A total of 3 comparative proteomic experiments were performed, comparing protein expression between chemotherapy-sensitive and chemotherapy-resistant oestrogen receptor-positive invasive ductal carcinoma tissue samples. This identified a list of 132 unique proteins that were significantly differentially expressed (≥ 2 fold) in chemotherapy resistant samples, 57 of which were identified in at least two experiments. Ingenuity® Pathway Analysis was used to map the 57 DEPs onto canonical signalling pathways. We implicate several isoforms of 14-3-3 family proteins (theta/tau, gamma, epsilon, beta/alpha and zeta/delta), which have previously been associated with chemotherapy resistance in breast cancer. Extensive clinical validation is now required to fully assess the role of these proteins as putative markers of chemotherapy response in luminal breast cancer subtypes.
新辅助化疗用于治疗雌激素受体阳性乳腺癌，但化疗耐药是这种分子亚型的主要障碍。预测肿瘤反应的能力将使化疗能够针对最受益的患者进行，从而最大限度地提高治疗效果。我们旨在使用比较 2-DE MALDI TOF/TOF MS 蛋白质组学分析乳腺癌肿瘤样本，在一项初步研究中鉴定与新辅助化疗反应相关的蛋白质生物标志物。共进行了 3 项比较蛋白质组学实验，比较了化疗敏感和化疗耐药的雌激素受体阳性浸润性导管癌组织样本之间的蛋白质表达。这确定了一组 132 种独特的蛋白质，它们在化疗耐药样本中差异表达（≥ 2 倍），其中 57 种在至少两个实验中被鉴定。Ingenuity®Pathway Analysis 被用于将 57 个 DEP 映射到经典信号通路。我们暗示了几种 14-3-3 家族蛋白（theta/tau、gamma、epsilon、beta/alpha 和 zeta/delta）的同工型，它们以前与乳腺癌的化疗耐药有关。现在需要进行广泛的临床验证，以充分评估这些蛋白质作为 luminal 乳腺癌亚型化疗反应的潜在标志物的作用。
