A gene expression signature for high-risk multiple myeloma

作者：Kuiper R; Broyl A; de Knegt Y; van Vliet M H; van Beers E H; van der Holt B; el Jarari L; Mulligan G; Gregory W; Morgan G; Goldschmidt H; Lokhorst H M; van Duin M; Sonneveld P^*

来源：Leukemia, 2012, 26(11): 2406-2413.

DOI：10.1038/leu.2012.127

• multiple myeloma
• gene expression
• signature
• prognosis
• survival
• comparison

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%26lt;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.

• 出版日期2012-11