近日，英國赫爾大學(xué)研究人員鑒定出可能有助于預(yù)測乳腺癌患者化療耐藥的生物標(biāo)志物,。
化療耐藥是乳腺癌治療的主要問題,，許多癌癥患者對化療藥物并不起反應(yīng)?；熌退幫鶗沟闷渌线m的治療手段延后,，病人接受治療后都會有某些類型的副作用。
發(fā)表在《蛋白質(zhì)組學(xué)》雜志上的文章表明，Hull研究人員已經(jīng)鑒定一些抵抗常見的化療藥物包括表阿霉素和多西紫杉醇等相關(guān)的潛在生物標(biāo)志物,。
研究領(lǐng)導(dǎo)者Lynn Cawkwell博士說：癌癥研究的主要目標(biāo)是能夠預(yù)測患者對化療的反應(yīng),，不幸的是，可靠的測試尚未被開發(fā)以實(shí)現(xiàn)這一目標(biāo),，我們希望我們的工作可以讓我們更近這一目標(biāo),。
大部分研究工作使用的是臨床標(biāo)本，而不是細(xì)胞系,。因?yàn)橛捎谘芯咳藛T與赫爾城山醫(yī)院的腫瘤學(xué)家和醫(yī)生有聯(lián)系,。研究用的臨床樣本給出了與實(shí)際疾病有關(guān)的更加準(zhǔn)確的基因表述表達(dá)情況。
該研究采用兩個高通量技術(shù)篩選臨床乳腺腫瘤組織樣本,。
一個使用抗體篩查方法,，鑒定出38個蛋白質(zhì)標(biāo)志物，這些蛋白質(zhì)在抗化療藥物的乳腺癌患者上的表達(dá)是那些耐化療的癌癥患者的樣本的兩倍,。另一種篩查方法采用質(zhì)譜,，共鑒定出57個潛在蛋白標(biāo)志物，其中5個屬于14-3-3蛋白家族,。
兩種篩查方法的研究結(jié)果從14-3-3家庭發(fā)現(xiàn)的蛋白質(zhì)可能發(fā)展成臨床預(yù)測檢測指標(biāo),。Cawkwell博士團(tuán)隊(duì)希望能更充分地探討該蛋白家族在化療耐藥中的作用。
她說：如果我們是正確的,，我們希望通過檢測這些蛋白質(zhì),，醫(yī)生能夠預(yù)見到不同化療病人的反應(yīng)，并決定哪種療程是最適合患者的,。（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.
