维吾尔族妇女宫颈癌特异性早期预警指标的血浆蛋白质组学研究
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摘要
目的：蛋白质是基因表达调控的较高层次产物,而疾病发生相关的蛋白质动态变化的信息可能融入血液之中。本研究依托蛋白质二维液相色谱技术,分析维吾尔族妇女宫颈鳞癌早期患者特异性血浆低丰度蛋白质组指纹图谱特征,拟建立肿瘤临床早期特异的血浆蛋白组谱鉴别模型,为血浆蛋白标志物的进一步鉴定及早期预警体系的建立提供客观依据。方法：收集维吾尔族妇女血浆标本共48例,包括慢性宫颈炎患者22例,临床分期为Ⅰ-Ⅱa的宫颈鳞癌早期患者26例；利用高丰度蛋白去除方法,制备血浆低丰度蛋白质组样品,通过蛋白质二维液相色谱系统(ProteomeLabTM PF-2D)分离与分析,以及专业软件数据处理,研究宫颈癌早期和宫颈炎患者蛋白质组特征,建立宫颈癌早期患者特异的血浆蛋白质组鉴别模型。结果：通过血浆低丰度蛋白组的二维液相色谱分析,确定了宫颈炎和宫颈鳞癌早期患者的血浆低丰度蛋白质组图谱特征,建立了宫颈癌早期患者特异性血浆蛋白质组指纹图谱差异鉴别模型。以2倍以上的血浆蛋白质含量变化作为蛋白质峰组分的定量差异标准,并将宫颈炎患者设为对照,综合分析二组的有效蛋白组分,发现有9个差异组分,宫颈鳞癌早期患者血浆中8个低丰度蛋白组分含量明显上升,而1个组分含量下降。结论：蛋白质二维液相色谱技术作为一种高通量技术手段在血浆蛋白质组学研究中有很大应用潜力。本研究发现维吾尔族妇女宫颈鳞癌早期患者与慢性宫颈炎患者之间存在血浆低丰度蛋白质组差异,为进一步鉴定肿瘤发生有关的血浆标志蛋白以及肿瘤早期诊断提供了客观依据。
Objective:Protein is a relatively high level product of gene expression control and the information on proteins dynamically altered by disease may be found in blood. In this study, fingerprint features of low abundant plasma proteome specific to early stage cervical squamous cell carcinoma in Uighur women was analyzed by two dimensional liquid phase chromatography. A plasma proteomic model to distinguish patients of early clinical stage tumor from the normal was established, and to provide evidences for further identification of plasma protein markers and establishment of early warning system as well.
Methods:48 cases of plasma samples from Uighur women was collected, including 22 cases of cervicitis and 26 cases of early stage cancer at clinical stageⅠ-Ⅱa; After preparation of low abundant plasma proteome by depletion of high abundant plasma proteins, the proteomic fingerprint features of patients with early stage cancer and cervicitis were studied by separation and analysis of the plasma proteome with two dimensional liquid phase chromatography and to establish a distinguishing model of plasma proteome for patients with early stage cancer subsequent data processed with professional software.
Results:The features of low abundant plasma proteome of patients with early stage cancer and cervicitis was studied by two dimensional liquid phase chromatography and a plasma proteome fingerprint model specific to patients with early stage cancer was established. By setting up the protein content difference of more than two times as a standard for quantitative differences,8 peaks with ascending and 1 with descending protein content in patients with early stage of cancer compared to cervicitis were found.
Conclusion:The two-dimensional liquid phase chromatography as a high throughput method has a promising application potential in the research of plasma proteomics. The remarkable differences in low abundant plasma proteomes between early stages of cervical squamous cell carcinoma (CSCC) and cervicitis in Uighur women may provide an important evidence for the identification of plasma protein markers of the cancer development and early diagnosis in the future.
Objective:Protein is a relatively high level product of gene expression control and the information on proteins dynamically altered by disease may be found in blood. In this study, fingerprint features of low abundant plasma proteome specific to early stage cervical squamous cell carcinoma in Uighur women was analyzed by two dimensional liquid phase chromatography. A plasma proteomic model to distinguish patients of early clinical stage tumor from the normal was established, and to provide evidences for further identification of plasma protein markers and establishment of early warning system as well.
Methods:48 cases of plasma samples from Uighur women was collected, including 22 cases of cervicitis and 26 cases of early stage cancer at clinical stageⅠ-Ⅱa; After preparation of low abundant plasma proteome by depletion of high abundant plasma proteins, the proteomic fingerprint features of patients with early stage cancer and cervicitis were studied by separation and analysis of the plasma proteome with two dimensional liquid phase chromatography and to establish a distinguishing model of plasma proteome for patients with early stage cancer subsequent data processed with professional software.
Results:The features of low abundant plasma proteome of patients with early stage cancer and cervicitis was studied by two dimensional liquid phase chromatography and a plasma proteome fingerprint model specific to patients with early stage cancer was established. By setting up the protein content difference of more than two times as a standard for quantitative differences,8 peaks with ascending and 1 with descending protein content in patients with early stage of cancer compared to cervicitis were found.
Conclusion:The two-dimensional liquid phase chromatography as a high throughput method has a promising application potential in the research of plasma proteomics. The remarkable differences in low abundant plasma proteomes between early stages of cervical squamous cell carcinoma (CSCC) and cervicitis in Uighur women may provide an important evidence for the identification of plasma protein markers of the cancer development and early diagnosis in the future.
引文
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[1]Parkin D, Whelan S, Ferlay J,et al. Cancer incidence in five continents[M]. Vol. Ⅷ. Lyon:IARC Press,2002.
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[26]王英,赵晓航.血浆蛋白质组一人类蛋白质组计划的“探路者”[J].生物化学与生物物理进展,2004,31(8)：376.
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[2]Ferlay J, Autier P, Boniol M,et al. Estimates of the cancer incidence and mortality in Europe in 2006[J].Annals Oncol,2007,18:581-592.
[3]Ahmedin Jemal,Freddie Bray,Melissa M.Center,et al.Global Cancer Statistics[J]. CA Cancer J Clin,2011,61:1-22.
[4]李连弟,鲁凤珠,张思维等.中国恶性肿瘤死亡率20年变化趋势和近期预测分析[J].中华肿瘤杂志,1997,19(1)：3-9.
[5]杨玲,李连弟,陈育德等.中国肺癌死亡趋势分析及发病、死亡的估计与预测[J].中国肺癌杂志,2005,8(4)：274-278.
[6]马丁,奚玲.宫颈癌流行病学及病因学研究进展[J].实用妇产科杂志,2001,17：61-63.
[7]古扎丽努尔,彭芝兰,郭英.HPV及其亚型在四川西北地区汉族及新疆南部地区维吾尔族妇女宫颈癌组织中的差异表达[J].中华微生物学和免疫学杂志,2004,24(5)：406.
[8]拉莱·苏祖克,彭玉华,周康等.新疆不同民族宫颈癌发病趋势分析[J].新疆医科大学学报,2006,29(7)：569-571.
[9]张国庆,刘开江,赖小军等.新医大附属肿瘤医院1989-2002年住院病人恶性肿瘤分布[J].新疆医科大学学报,2003,26(4)：393-395.
[10]凌斌.宫颈癌诊断与治疗的新进展[J].中国实用妇科与产科杂志,2007,23(1)：23-25.
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