基于蛋白质组学技术筛查维吾尔族妇女宫颈癌前病变患者血浆蛋白预警标志物

 依托蛋白质二维液相色谱和质谱技术,寻找与新疆维吾尔族妇女宫颈癌癌前病变高度宫颈鳞状上皮内瘤样变(HSIL)相关的血浆预警蛋白标志物,旨在对宫颈癌做到早期预防和诊断。收集维吾尔族HSIL(21例)和宫颈炎(22例)患者血浆标本并制备血浆低丰度蛋白质组样品,通过对蛋白质二维液相色谱系统的分离与鉴别分析,筛选出差异表达的组分,并运用质谱和生物信息学技术进行鉴定和功能识别分析。确定了宫颈炎和HSIL患者的基于蛋白质等电点和疏水性特征的血浆低丰度蛋白质组图谱,筛选出10个差异表达蛋白组分。结果表明,在HSIL患者血浆中3个低丰度蛋白组分含量明显上升,1个组分含量下降;而通过质谱技术鉴定出31种蛋白质,其中4种蛋白质与肿瘤进程密切相关,分别是代谢相关蛋白(APOA1)、信号转导相关蛋白(mTOR、EphA3)和免疫功能相关蛋白(HLA-DQB1)。本文针对维吾尔族妇女这一宫颈癌高发人群,展开癌前病变患者血浆低丰度蛋白组表达水平的研究,鉴定出多种差异表达血浆蛋白预警标志物,为本区宫颈癌的预防和早期鉴别诊断及癌变机制研究提供了依据。

Early-warning Plasma Biomarkers Screening for the Uighur Women Patients with Cervical Precancerous Lesion Based on Proteomic Techniques

The early-warning plasma biomarkers screening of High-grade cervical Squamous Intraepithelial Lesion (HSIL) for the Uighur women patients by using two-dimensional liquid phase chromatography and mass spectrometry is aimed. The plasma samples from Uighur women with cervical lesions (21 cases with HSIL and 22 cases with cervicitis) were collected and low abundant plasma proteins were prepared. After the establishment of a differential proteome profile by two-dimensional liquid phase chromatography, mass spectrometry and bioinformatics technology were used to identify and analyze differential proteins. Based on the protein isoelectric point gradient and hydrophobic features of low abundant plasma proteins, a differential proteome profile was established for the Uighur women with cervicitis and HSIL; it is found that three peak constituents are upregulated and one is downregulated in the patients with HSIL. Identification of these proteins by mass spectrometry shows that a total of 31 plasma proteins are differentially expressed, four proteins that closely associated with tumor progress including metabolome-related proteins (APOA1), signal transduction-related proteins (mTOR, EphA3), and immune-related proteins (HLA-DQB1) are selected. By focusing on the early-warning low abundant plasma proteome biomarker of Uighur women with precancerous lesion, the evidence for prevention, early diagnosis, and canceration mechanism understanding of cervical cancer in Xinjiang Autonomous Region is provided.