title: Low-risk identification in multiple myeloma using a new 14-gene model.
abstract: Identifying the best gene expression pattern associated with low-risk disease in patients with newly diagnosed multiple myeloma (MM) is important to direct clinical treatments. The MM Survival Index14 (MMSI14) was developed from GEP data sets of 22 normal plasma cells (NPC), 5 MM cell lines (MMCL), 44 monoclonal gammopathy of undetermined significance (MGUS), and 351 newly diagnosed MM patients. R/bioconductor and siggenes package were used to obtain heatmap, boxplot and histogram whose results were then analyzed by Kaplan-Meier analysis. Fourteen genes associated with low-risk disease in MM were identified. We validated the disease prognostic power of MMSI14 with an independent data set of other 214 newly diagnosed MM patients and also compared our model with the 70-gene, the 8-subgroup, IFM15, and HMCLs7 models. Survival analysis showed that a low MMSI14 signature was associated with longer survival. Applying MMSI14 to independent data sets, we were able to classify 39% of patients as low-risk, with a survival probability of more than 90% at 60 months. Multiple clinical parameters confirmed significant correlation between low- and high-risk subgroups defined by MMSI14. Comparing previously published models to the same data sets the MMSI14 model retained the best prognostic value. We have developed a new gene model (MMSI14) for defining low-risk, newly diagnosed MM. The multivariate comparative analysis confirmed that MMSI14 is the best available model to predict clinical outcome in MM patients.
authors.affiliation: Molecular Medicine Program, University of Utah, Salt Lake City, Utah 84132, USA. tchen@u2m2.utah.edu
authors.forename: Tiehua
authors.initials: T
authors.lastname: Chen
authors.forename: Tamara
authors.initials: T
authors.lastname: Berno
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D012306:Risk