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A novel panel of protein biomarkers for predicting response to thalidomide-based therapy in newly diagnosed multiple myeloma patients.
MedLine Citation:
PMID:  21365752     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Multiple myeloma (MM) is a heterogeneous group of disorders both genotypically and phenotypically. Response to thalidomide-based induction therapy in newly diagnosed patients varies significantly in published clinical trials. Proteomic analysis was performed on 39 newly diagnosed MM patients treated with a thalidomide-based regimen (22 responders; 17 non-responders) using immunodepletion, 2-D DIGE analysis and mass spectrometry. Zinc-α-2-glycoprotein (ZAG), vitamin D-binding protein (VDB), serum amyloid-A protein (SAA) and β-2-microglobulin (B2M) had statistically significant higher concentrations in non-responders compared to responders, while haptoglobin (Hp) had a lower concentration. ELISAs were used to validate the candidate protein biomarkers using unfractionated serum from 51 newly diagnosed MM patients (29 responders; 22 non-responders). Using logistic regression, the best possible area under the curve (AUC) was 0.96 using ZAG, VDB and SAA in combination. Leave-one-out-cross-validation (LOOCV) indicated an overall predictive accuracy of 84% with associated sensitivity and specificity values of 81.8 and 86.2%, respectively. Subsequently, 16 of 22 thalidomide-refractory patients successfully achieved complete response or very good partial response using second-line treatment suggesting that the biomarker profile is specific to thalidomide response rather than identifying patients with MM refractory to all therapies. Using a novel panel of predictive biomarkers, the feasibility of predicting response to thalidomide-based therapy in previously untreated MM has been demonstrated.
Authors:
Rajesh Rajpal; Paul Dowling; Justine Meiller; Colin Clarke; William G Murphy; Robert O'Connor; Malcolm Kell; Constantine Mitsiades; Paul Richardson; Kenneth C Anderson; Martin Clynes; Peter O'Gorman
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-14
Journal Detail:
Title:  Proteomics     Volume:  -     ISSN:  1615-9861     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-3-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101092707     Medline TA:  Proteomics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
National Institute for Cellular Biotechnology (NICB), Dublin City University, Dublin, Ireland; Mater Misericordiae University Hospital, Dublin, Ireland; Irish Blood Transfusion Services, Dublin, Ireland.
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