4.6 Article

Evaluating gene expression profiling by quantitative polymerase chain reaction to develop a clinically feasible test for outcome prediction in multiple myeloma

Journal

BRITISH JOURNAL OF HAEMATOLOGY
Volume 163, Issue 2, Pages 223-234

Publisher

WILEY-BLACKWELL
DOI: 10.1111/bjh.12519

Keywords

Gene expression profile; quantitative PCR; multiple myeloma

Categories

Funding

  1. Spanish Instituto de Salud Carlos III (ISCIII) [PS09/01450, PI12/02311]
  2. Red Tematica de Investigacion Cooperativa en Cancer (RTICC) [RD12/0036/0069, RD12/0036/0058]
  3. Spanish Ministry of Economy and Competitiveness
  4. European Regional Development Fund (ERDF) Una manera de hacer Europa
  5. Consejeria de Educacion de la Junta de Castilla y Leon [HUS412A12-1]
  6. Asociacion Espanola Contra el Cancer [GCB-120981SAN]

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The gene expression profiles (GEPs) of 96 selected genes were analysed by real-time quantitative polymerase chain reaction (qPCR) with a TaqMan low-density array card in isolated tumour plasma cells (PCs) from 157 newly diagnosed multiple myeloma (MM) patients. This qPCR-based GEP correctly classified cases following the Translocation-cyclin D classification. Classic prognostic parameters and qPCR-based GEP predicted MM patient outcome and, although multivariate analyses revealed that cytogenetic risk (standard vs. high risk) was the variable that most strongly predicted prognosis, GEP added significant information for risk stratification. Considering only the standard risk cytogenetic patients, multivariate analyses revealed that high beta 2-microglobulin, low CDKN1A and high SLC19A1 gene expression levels independently predicted a short time-to-progression (TTP), while high International Staging System stage, low CDKN2B and high TBRG4 gene expression predicted poor overall survival (OS). A gene expression risk score enabled the division of standard risk patients into two groups with different TTPs (83% vs. 38% at 3years, P<0 center dot 0001) and OS rates (88% vs. 61% at 5years; P=0 center dot 003). This study demonstrates that quantitative PCR is a robust, accurate and feasible technique for implementing in the daily routine as a surrogate for GEP-arrays.

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