J Proteomics：化疗耐药乳腺癌的生物标志物

近日，英国赫尔大学研究人员鉴定出可能有助于预测乳腺癌患者化疗耐药的生物标志物。

化疗耐药是乳腺癌治疗的主要问题，许多癌症患者对化疗药物并不起反应。化疗耐药往往会使得其他更合适的治疗手段延后，病人接受治疗后都会有某些类型的副作用。

发表在《蛋白质组学》杂志上的文章表明，Hull研究人员已经鉴定一些抵抗常见的化疗药物包括表阿霉素和多西紫杉醇等相关的潜在生物标志物。

研究领导者Lynn Cawkwell博士说：癌症研究的主要目标是能够预测患者对化疗的反应，不幸的是，可靠的测试尚未被开发以实现这一目标，我们希望我们的工作可以让我们更近这一目标。

大部分研究工作使用的是临床标本，而不是细胞系。因为由于研究人员与赫尔城山医院的肿瘤学家和医生有联系。研究用的临床样本给出了与实际疾病有关的更加准确的基因表述表达情况。

该研究采用两个高通量技术筛选临床乳腺肿瘤组织样本。

一个使用抗体筛查方法，鉴定出38个蛋白质标志物，这些蛋白质在抗化疗药物的乳腺癌患者上的表达是那些耐化疗的癌症患者的样本的两倍。另一种筛查方法采用质谱，共鉴定出57个潜在蛋白标志物，其中5个属于14-3-3蛋白家族。

两种筛查方法的研究结果从14-3-3家庭发现的蛋白质可能发展成临床预测检测指标。Cawkwell博士团队希望能更充分地探讨该蛋白家族在化疗耐药中的作用。

她说：如果我们是正确的，我们希望通过检测这些蛋白质，医生能够预见到不同化疗病人的反应，并决定哪种疗程是最适合患者的。（生物谷：Bioon.com）

doi:10.1016/j.jprot.2012.03.049
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Pilot and feasibility study: comparative proteomic analysis by 2-DE MALDI TOF/TOF MS reveals 14-3-3 proteins as putative biomarkers of response to neoadjuvant chemotherapy in ER-positive breast cancer

Victoria C. Hodgkinsona, Vijay Agarwala, b, c, Dalia ELFadla, d, John N. Foxd, Penelope L. McManusd, Tapan K. Mahapatrad, Peter J. Kneeshawd, Philip J. Drewa, b, d, Michael J. Linda, b, c, Lynn Cawkwella, b

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.