He Jianbo, Whelan Stephen A, Lu Ming, Shen Dejun, Chung Debra U, Saxton Romaine E, Faull Kym F, Whitelegge Julian P, Chang Helena R
Gonda/UCLA Breast Cancer Research Laboratory, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Int J Proteomics. 2011;2011:896476. doi: 10.1155/2011/896476. Epub 2011 Oct 24.
Protein-based markers that classify tumor subtypes and predict therapeutic response would be clinically useful in guiding patient treatment. We investigated the LC-MS/MS-identified protein biosignatures in 39 baseline breast cancer specimens including 28 HER2-positive and 11 triple-negative (TNBC) tumors. Twenty proteins were found to correctly classify all HER2 positive and 7 of the 11 TNBC tumors. Among them, galectin-3-binding protein and ALDH1A1 were found preferentially elevated in TNBC, whereas CK19, transferrin, transketolase, and thymosin β4 and β10 were elevated in HER2-positive cancers. In addition, several proteins such as enolase, vimentin, peroxiredoxin 5, Hsp 70, periostin precursor, RhoA, cathepsin D preproprotein, and annexin 1 were found to be associated with the tumor responses to treatment within each subtype. The MS-based proteomic findings appear promising in guiding tumor classification and predicting response. When sufficiently validated, some of these candidate protein markers could have great potential in improving breast cancer treatment.
能够对肿瘤亚型进行分类并预测治疗反应的蛋白质标志物在指导患者治疗方面具有临床实用性。我们研究了39份基线乳腺癌标本中经液相色谱-串联质谱(LC-MS/MS)鉴定的蛋白质生物标志物,其中包括28例HER2阳性肿瘤和11例三阴性(TNBC)肿瘤。发现有20种蛋白质能够正确分类所有HER2阳性肿瘤以及11例TNBC肿瘤中的7例。其中,半乳糖凝集素-3结合蛋白和醛脱氢酶1A1(ALDH1A1)在TNBC中优先升高,而细胞角蛋白19(CK19)、转铁蛋白、转酮醇酶以及胸腺素β4和β10在HER2阳性癌症中升高。此外,还发现烯醇化酶、波形蛋白、过氧化物酶5、热休克蛋白70(Hsp 70)、骨膜蛋白前体、RhoA、组织蛋白酶D前体蛋白和膜联蛋白1等几种蛋白质与各亚型肿瘤的治疗反应相关。基于质谱的蛋白质组学研究结果在指导肿瘤分类和预测反应方面似乎很有前景。经过充分验证后,其中一些候选蛋白质标志物在改善乳腺癌治疗方面可能具有巨大潜力。