Rajpal, Rajesh and Dowling, Paul and Meiller, Justine and Clarke, Colin and Murphy, William G. and O'Connor, Robert and Kell, Malcolm and Mitsiades, Constantine and Richardson, Paul and Anderson, Kenneth C. and Clynes, Martin and O'Gorman, Peter (2011) A novel panel of protein biomarkers for predicting response to thalidomide-based therapy in newly diagnosed multiple myeloma patients. Proteomics, 11 (8). pp. 1391-1402. ISSN 1615-9853

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Abstract

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-a-2-glycoprotein (ZAG), vitamin D-binding protein (VDB), serum amyloid-A protein (SAA) and b-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.

Item Type:	Article
Keywords:	Biomarkers; Biomedicine; Multiple myeloma; Thalidomide;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	7348
Identification Number:	https://doi.org/10.1002/pmic.201000471
Depositing User:	Paul Dowling
Date Deposited:	16 Aug 2016 15:46
Journal or Publication Title:	Proteomics
Publisher:	Wiley
Refereed:	Yes
URI:	http://onlinelibrary.wiley.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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