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首页> 外文期刊>Expert opinion on investigational drugs >Changes in protein expression after neoadjuvant use of aromatase inhibitors in primary breast cancer: a proteomic approach to search for potential biomarkers to predict response or resistance
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Changes in protein expression after neoadjuvant use of aromatase inhibitors in primary breast cancer: a proteomic approach to search for potential biomarkers to predict response or resistance

机译：新辅助使用芳香化酶抑制剂后在原发性乳腺癌中蛋白质表达的变化：一种蛋白质组学方法来寻找潜在的生物标志物以预测反应或耐药

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Objective: Aromatase inhibitors (AI) have been established as a useful hormonal therapy in hormone receptor-expressing breast carcinoma. However, changes in tumor protein expression after exposure to AIs are not necessarily well understood. These changes may provide insight into how breast carcinomas respond or develop into a state of resistance towards AIs, and lead to the discovery of potential biomarkers to predict treatment responses. Methods: Post-menopausal breast cancer patients were recruited to receive 3 months treatment with neoadjuvant AI. Carcinoma tissues were collected before and after the use of AIs and protein expression profiles were compared using two-dimensional gel electrophoresis. Protein spots with different levels of expression were identified using mass spectrometry. Results: A total of 14 matched pairs of tumor tissues were collected. Both up-regulated and down-regulated proteins were selected and identified as follows: heat shock protein 70 protein 2; Cyclin M3, alpha 1 antichymotrypsin precursor; carbonic anhydrase I, cancer antigen 1; SOBP protein; Rho GDP dissociation inhibitor alpha; glyoxalase I with benzyl glutathione inhibitor; lipid-free human apolipoprotein A-I and RAB4A member RAS oncogene family. Among these proteins, heat shock protein 70 demonstrated the most significant positive correlation with clinical response of the patients. Conclusion: After neoadjuvant use of AI, heat shock protein 70 demonstrated the most consistent phenotypic consistency in both up-regulated and down-regulated protein expression levels among the 14 studied pairs of tumor tissue. Other proteins worthwhile exploring were also identified in this study. These proteins could serve as potential predictors for AI response.
机译：目的：芳香酶抑制剂（AI）已被确立为表达激素受体的乳腺癌的有效激素疗法。但是，未必充分了解暴露于AIs后肿瘤蛋白表达的变化。这些变化可以提供关于乳腺癌如何反应或发展成对AI耐药的状态的见解，并导致发现潜在的生物标记物以预测治疗反应。方法：招募绝经后乳腺癌患者接受新辅助AI治疗3个月。在使用AI之前和之后收集癌组织，并使用二维凝胶电泳比较蛋白质表达谱。使用质谱鉴定具有不同表达水平的蛋白质斑点。结果：总共收集到14对匹配的肿瘤组织。选择上调和下调的蛋白，并鉴定如下：热激蛋白70蛋白2;热激蛋白70。 Cyclin M3，α1抗胰凝乳蛋白酶前体;碳酸酐酶I，癌症抗原1; SOBP蛋白; Rho GDP离解抑制剂alpha;乙二醛酶I与苄基谷胱甘肽抑制剂;无脂人类载脂蛋白A-1和RAB4A成员RAS癌基因家族。在这些蛋白中，热休克蛋白70与患者的临床反应表现出最显着的正相关。结论：在新辅助使用AI后，在研究的14对肿瘤组织中，热激蛋白70在上调和下调蛋白表达水平上表现出最一致的表型一致性。在这项研究中还鉴定了其他值得探索的蛋白质。这些蛋白质可以作为AI反应的潜在预测因子。

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