ER/PR阳性和阴性乳腺癌的定量蛋白质组学和生物信息学比较研究

目的:建立雌/孕激素受体(ER/PR)阴性和阳性乳腺癌的蛋白质表达谱,寻找ER/PR阴性和阳性乳腺癌中差异表达蛋白,为乳腺癌患者提供新的预后预测指标和治疗新靶点。方法:应用蛋白质组学i TRAQ技术建立ER/PR阳性和阴性乳腺癌的蛋白质差异表达谱,鉴定两组乳腺癌的差异表达蛋白,对部分差异表达蛋白进行生物信息学分析,包括蛋白功能注释和分类GO分析和KEGG通路分析。结果:应用i TRAQ蛋白质组学技术对乳腺癌组织进行了蛋白组学分析,鉴定出ER/PR阳性和阴性组间有差异表达的蛋白4999种,以ER/PR阳性:ER/PR阴性≥3为上调标准,确定ER/PR阳性组上调蛋白101种。以ER/PR阳性:ER/PR阴性≤0.5为下调标准,ER/PR阳性组下调蛋白122种。GO分析结果显示ER/PR受体阴性和阳性乳腺癌的差异表达蛋白的分子功能、生物过程、细胞定位较为复杂,并且在上调蛋白和下调蛋白上存在分布差异。KEGG通路分析发现部分差异表达蛋白涉及201条信号通路。结论:ER/PR阳性和阴性乳腺癌间存在差异表达蛋白,这些蛋白涉及复杂的分子功能、生物过程和信号通路。

Comparative Quantitative Proteomic and Bioinformatics Study on ER/PR Positive and Negative Breast Cancer

Objective:To establish differentially expressed proteins profiles for ER/PR negative and positive breast cancer and provide new prognostic markers and therapeutic targets for patients with ER/PR positive breast cancer.Methods:By proteomic iTRAQ technology, ER/PR positive and negative breast cancer protein expression profiles was established, differences of protein expression were identified and parts of differential expression protein by bioinformatics analysis, including protein function annotation and GO classification analysis and KEGG pathway analysis.Results:iTRAQ proteomic analysis of breast cancer tissue with identified ER/PR positive and negative groups showed 4999 differentially expressed protein. While Ratio of ER/PR(+) /ER/PR (-) was higher than or equal to 3 for standard cut, 101 up-regulated proteins in ER/PR positive group were identified. In ER/PR(+)/ER/PR (-) less than or equal to 0.5 for standard cut, 122 down-regulated proteins were identified in ER/PR positive group. The results of GO analysis showed that the cellular composition, molecular function, biological process of differentially expressed proteins were complex between ER/PR positive and negative breast cancer, and there were differences in the distribution of up-regulated proteins and down-regulation of proteins. KEGG pathway analysis showed that differentially expressed proteins involved in 201 signal pathways.Conclusion:There were differentially expressed proteins between ER/PR positive and negative breast cancer, which involved complex molecular function, biological process and signaling pathway.