首页 | 本学科首页   官方微博 | 高级检索  
     


Prostate cancer serum biomarker discovery through proteomic analysis of alpha‐2 macroglobulin protein complexes
Authors:Earle F Burgess  Amy‐Joan L Ham  David L Tabb  Dean Billheimer  Bruce J Roth  Sam S Chang  Michael S Cookson  Timothy J Hinton  Kristin L Cheek  Salisha Hill  Jennifer A Pietenpol Dr
Affiliation:1. Vanderbilt‐Ingram Cancer Center, 777 PRB, Vanderbilt University School of Medicine, Nashville, TN, USA;2. Department of Medicine, D3100 MCN, Vanderbilt University School of Medicine, Nashville, TN, USA;3. Mass Spectrometry Research Center, 9144C MRBIII, Vanderbilt University School of Medicine, Nashville, TN, USA;4. Department of Biochemistry, 652 PRB, Vanderbilt University School of Medicine, Nashville, TN, USA;5. Department of Biomedical Informatics, 400 EBL, Vanderbilt University School of Medicine, Nashville, TN, USA;6. Department of Biostatistics, 571 PRB, Vanderbilt University School of Medicine, Nashville, TN, USA;7. Department of Urologic Surgery, A1302 MCN Vanderbilt University School of Medicine, Nashville, TN, USA
Abstract:Alpha‐2 macroglobulin (A2M) functions as a universal protease inhibitor in serum and is capable of binding various cytokines and growth factors. In this study, we investigated if immunoaffinity enrichment and proteomic analysis of A2M protein complexes from human serum could improve detection of biologically relevant and novel candidate protein biomarkers in prostate cancer. Serum samples from six patients with androgen‐independent, metastatic prostate cancer and six control patients without malignancy were analyzed by immunoaffinity enrichment of A2M protein complexes and MS identification of associated proteins. Known A2M substrates were reproducibly identified from patient serum in both cohorts, as well as proteins previously undetected in human serum. One example is heat shock protein 90 alpha (HSP90α), which was identified only in the serum of cancer patients in this study. Using an ELISA, the presence of HSP90α in human serum was validated on expanded test cohorts and found to exist in higher median serum concentrations in prostate cancer (n = 18) relative to control (n = 13) patients (median concentrations 50.7 versus 27.6 ng/mL, respectively, p = 0.001). Our results demonstrate the technical feasibility of this approach and support the analysis of A2M protein complexes for proteomic‐based serum biomarker discovery.
Keywords:Biomarker  Heat‐shock protein 90  Prostate cancer  Serum
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号