Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, United States.
J Proteome Res. 2012 Apr 6;11(4):2236-46. doi: 10.1021/pr201018y. Epub 2012 Mar 28.
Progression of invasive carcinoma involves the deregulation of molecular signaling pathways that results in the acquisition of oncogenic phenotypes. Functional enrichment analysis allows for the identification of deregulated pathways from omics scale expression data. Given the importance of post-transcriptional regulatory mechanisms on protein expression and function, identification of deregulated pathways on the basis of protein expression data is likely to provide new insights. In this study, we have developed methods for label-based mass spectrometry in a large number of samples and applied these methods toward identification and quantification of protein expression in samples of infiltrating ductal carcinoma, benign breast growths, and normal adjacent tissue. We identified 265 proteins with differential expression patterns in infiltrating ductal carcinoma relative to benign growths or normal breast tissue. Analysis of the differentially expressed proteins indicated the deregulation of signaling pathways related to proliferation, invasion and metastasis, and immune response. Our approach provides complementary information to gene expression microarray data and identifies a number of deregulated molecular signaling pathways indicative of breast cancer progression that may enable more accurate, biologically relevant diagnoses and provide a stepping stone to personalized treatment.
浸润性导管癌的进展涉及分子信号通路的失调，导致致癌表型的获得。功能富集分析允许从组学规模的表达数据中识别失调的途径。鉴于转录后调节机制对蛋白质表达和功能的重要性，基于蛋白质表达数据识别失调途径可能提供新的见解。在这项研究中，我们开发了大量样品中基于标签的质谱方法，并将这些方法应用于浸润性导管癌、良性乳腺生长和正常邻近组织样品中蛋白质表达的鉴定和定量。我们在浸润性导管癌相对于良性生长或正常乳腺组织中鉴定出 265 种具有差异表达模式的蛋白质。差异表达蛋白的分析表明，与增殖、侵袭和转移以及免疫反应相关的信号通路失调。我们的方法提供了基因表达微阵列数据的补充信息，并鉴定出许多表明乳腺癌进展的失调分子信号通路，这可能使诊断更准确、更具生物学相关性，并为个性化治疗提供一个起点。
