A gene expression signature for high-risk multiple myeloma
There is a strong need to better predict the survival of patients with newly diagnosed multiple myeloma (MM). As gene expression profiles (GEPs) reflect the biology of MM in individual patients, we built a prognostic signature based on GEPs. GEPs obtained from newly diagnosed MM patients included in...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
08 May 2012
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| In: |
Leukemia
Year: 2012, Volume: 26, Issue: 11, Pages: 2406-2413 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2012.127 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/leu.2012.127 Verlag, Volltext: https://www.nature.com/articles/leu2012127 
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| Author Notes: | R. Kuiper, A. Broyl, Y. de Knegt, M.H. van Vliet, E.H. van Beers, B. van der Holt, L. el Jarari, G. Mulligan, W. Gregory, G. Morgan, H. Goldschmidt, H.M. Lokhorst, M. van Duin and P. Sonneveld |
| Summary: | There is a strong need to better predict the survival of patients with newly diagnosed multiple myeloma (MM). As gene expression profiles (GEPs) reflect the biology of MM in individual patients, we built a prognostic signature based on GEPs. GEPs obtained from newly diagnosed MM patients included in the HOVON65/GMMG-HD4 trial (n=290) were used as training data. Using this set, a prognostic signature of 92 genes (EMC-92-gene signature) was generated by supervised principal component analysis combined with simulated annealing. Performance of the EMC-92-gene signature was confirmed in independent validation sets of newly diagnosed (total therapy (TT)2, n=351; TT3, n=142; MRC-IX, n=247) and relapsed patients (APEX, n=264). In all the sets, patients defined as high-risk by the EMC-92-gene signature show a clearly reduced overall survival (OS) with a hazard ratio (HR) of 3.40 (95% confidence interval (CI): 2.19-5.29) for the TT2 study, 5.23 (95% CI: 2.46-11.13) for the TT3 study, 2.38 (95% CI: 1.65-3.43) for the MRC-IX study and 3.01 (95% CI: 2.06-4.39) for the APEX study (P<0.0001 in all studies). In multivariate analyses this signature was proven to be independent of the currently used prognostic factors. The EMC-92-gene signature is better or comparable to previously published signatures. This signature contributes to risk assessment in clinical trials and could provide a tool for treatment choices in high-risk MM patients. |
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| Item Description: | Gesehen am 22.11.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2012.127 |