国际肿瘤学杂志

国际肿瘤学杂志 ›› 2016, Vol. 43 ›› Issue (10): 721-727.doi: 10.3760/cma.j.issn.1673-422X.2016.10.001

• 论著 •    下一篇

HER-2阳性和阴性乳腺癌中差异表达蛋白的定量蛋白质组学初步研究

李晶,黄三钱,欧阳取长,钟晶敏,高妮娜,刘莉萍,刘志红,曾亮   

  1. 410013 长沙，湖南省肿瘤医院&中南大学湘雅医学院附属肿瘤医院乳腺内科（李晶、欧阳取长、刘莉萍），病理科（黄三钱、钟晶敏、高妮娜、刘志红、曾亮）
  • 出版日期:2016-10-08 发布日期:2016-09-07
  • 通讯作者: 曾亮 E-mail:zlxx03@126.com
  • 基金资助:

    湖南省科学技术厅科技计划（2014FJ6090）

Preliminary study on quantitative proteomic analysis of differentially expressed proteins in HER-2 positive and negative breast cancer

Li Jing, Huang Sanqian, Ouyang Quchang, Zhong Jingmin, Gao Nina, Liu Liping, Liu Zhihong, Zeng Liang   

  1. Breast Department of Internal Medicine, Hunan Cancer Hospital ﹠ Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
  • Online:2016-10-08 Published:2016-09-07
  • Contact: Zeng Liang E-mail:zlxx03@126.com
  • Supported by:

    Science and Technology Project of Science and Technology Department of Hunan Province of China (2014FJ6090)

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摘要： 目的通过建立人表皮生长因子受体-2(HER-2)阴性和阳性乳腺癌的蛋白质表达谱寻找二者间的差异表达蛋白，为乳腺癌患者提供新的预后指标和治疗靶点。方法应用蛋白质组学同位素相对标记与绝对定量（iTRAQ）技术建立HER2阳性和阴性乳腺癌的蛋白质差异表达谱，分离并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、京都基因与基因组百科全书（KEGG）通路分析。结果应用iTRAQ对乳腺癌组织进行蛋白组学分析，鉴定出HER-2阳性和阴性组有差异表达的蛋白4 999种，以HER-2(+)/HER-2(－)≥3为上调标准，确定HER2阳性组上调蛋白119种。以HER-2(+)/HER-2(－)≤0.5为下调标准，HER-2阳性组下调蛋白47种。GO分析结果显示HER-2阴性和阳性乳腺癌的差异表达蛋白的分子功能、生物过程、细胞组成较为复杂，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168条信号通路。结论HER-2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。

关键词: 乳腺肿瘤, 受体, 表皮生长因子, 蛋白质组学, 计算生物学

Abstract: ObjectiveTo seek differentially expressed proteins for human epithelial growth factor receptor2 (HER2) negative and positive breast carcinoma through establishing proteins profiles, and to provide new prognostic markers and therapeutic targets for patients with breast cancer. MethodsHER2 positive and negative breast cancer protein expression profiles were established using proteomic isobaric tags for relative and absolute quantitation (iTRAQ) technology. Differences of protein expression were identified and parts of differential expression proteins were analyzed by bioinformatics, including protein function annotation and GO classification analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis. ResultsProteomic analysis of breast cancer tissue with identified HER2 positive and negative groups showed 4 999 differentially expressed proteins by iTRAQ. Based on the criteria of the ratio of HER2(+)/HER2(－)≥3, 119 upregulated proteins were identified in HER2 positive group. Based on the criteria of the ratio of HER2(+)/HER2(－)≤0.5, 47 downregulated proteins were identified in HER2 positive group. The results of GO analysis showed that the molecular function, biological process and cellular composition of differentially expressed proteins were complex between HER2 positive and negative breast cancer. 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 168 signal pathways. ConclusionThere are differentially expressed proteins between HER2 positive and negative breast cancer, which involve complex molecular function, biological process and signaling pathway.

Key words: Breast neoplasms, Receptor, epidermal growth factor, Proteomics, Computational biology