Improving knowledge on the activation of bone marrow fibroblasts in MGUS and MM disease through the automatic extraction of genes via a nonnegative matrix factorization approach on gene expression profiles

Multiple myeloma (MM) is a cancer of terminally differentiated plasma that is part of a spectrum of blood diseases. The role of the micro-environment is crucial for MM clonal evolution. This paper describes the analysis carried out on a limited number of genes automatically extracted by a nonnegative matrix factorization (NMF) based approach from gene expression profiles of bone marrow fibroblasts of patients with monoclonal gammopathy of undetermined significance (MGUS) and MM. Automatic exploration through NMF, combined with a motivated post-processing procedure and a pathways analysis of extracted genes, allowed to infer that a functional switch is required to lead fibroblasts to acquire pro-tumorigenic activity in the progression of the disease from MGUS to MM. The extracted biologically relevant genes may be representative of the considered clinical conditions and may contribute to a deeper understanding of tumor behavior.