Wang David L, Xiao Chuanguang, Fu Guofeng, Wang Xing, Li Liang
Department of Biology, Vanderbilt University, Nashville, TN USA.
Zibo Central Hospital, Zibo, China.
Biomark Res. 2017 Mar 14;5:11. doi: 10.1186/s40364-017-0092-9. eCollection 2017.
Cancer is a genetic disease; its development and metastasis depend on the function of many proteins. Human serum contains thousands of proteins; it is a window for the homeostasis of individual's health. Many of the proteins found in the human serum could be potential biomarkers for cancer early detection and drug efficacy evaluation.
In this study, a functional proteomics technology was used to systematically monitor metabolic enzyme and protease activities from resolved serum proteins produced by a modified 2-D gel separation and subsequent Protein Elution Plate, a method collectively called PEP. All the experiments were repeated at least twice to ensure the validity of the findings.
For the first time, significant differences were found between breast cancer patient serum and normal serum in two families of enzymes known to be involved in cancer development and metastasis: metabolic enzymes and proteases. Multiple enzyme species were identified in the serum assayed directly or after enrichment. Both qualitative and quantitative differences in the metabolic enzyme and protease activity were detected between breast cancer patient and control group, providing excellent biomarker candidates for breast cancer diagnosis and drug development.
This study identified several potential functional protein biomarkers from breast cancer patient serum. It also demonstrated that the functional proteomics technology, PEP, can be applied to the analysis of any functional proteins in human serum which contains thousands of proteins. The study indicated that the functional domain of the human serum could be unlocked with the PEP technology, pointing to a novel alternative for the development of diagnosis biomarkers for breast cancer and other diseases.
癌症是一种基因疾病;其发展和转移取决于多种蛋白质的功能。人血清含有数千种蛋白质;它是个体健康稳态的一个窗口。在人血清中发现的许多蛋白质可能是癌症早期检测和药物疗效评估的潜在生物标志物。
在本研究中,一种功能蛋白质组学技术被用于系统监测由改良的二维凝胶分离及后续的蛋白质洗脱板(一种统称为PEP的方法)产生的已分离血清蛋白中的代谢酶和蛋白酶活性。所有实验至少重复两次以确保研究结果的有效性。
首次在已知参与癌症发展和转移的两类酶,即代谢酶和蛋白酶方面,发现乳腺癌患者血清与正常血清之间存在显著差异。在直接检测或富集后的血清中鉴定出了多种酶。在乳腺癌患者和对照组之间检测到了代谢酶和蛋白酶活性的定性和定量差异,为乳腺癌诊断和药物开发提供了优秀的生物标志物候选物。
本研究从乳腺癌患者血清中鉴定出了几种潜在的功能性蛋白质生物标志物。它还证明了功能蛋白质组学技术PEP可应用于分析人血清中包含数千种蛋白质的任何功能性蛋白质。该研究表明,PEP技术可以开启人血清功能领域的研究,为乳腺癌和其他疾病诊断生物标志物的开发指出了一种新的选择。